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Price: $2,915

  • Number of Genes Included: 45
    Acceptable Sample Types:

    • Blood (3-6ml EDTA)
    • Saliva (Oragene 500 or 600)
    • Cultured Fibroblasts (T75 flask)
    • Extracted DNA (extracted from a CLIA-certified lab)

    Price: $2,915
    CPT Code: 81479
    Turnaround Time: 6-8 weeks
    Platform: Exome + del/dup analysis

    GenesALPL, ALX1, ALX3, ALX4, CDC45, CYP26B1, DHODH, EFNB1, EFTUD2, ERF, FBN1, FGFR1, FGFR2, FGFR3, FREM1, GLI3, IFT122, IFT43, IHH, IL11RA, KRAS, MASP1, MEGF8, MSX2, P4HB, PHF6, PHF8, POLR1C, POLR1D, POR, RAB23, RECQL4, RSPRY1, SEC24D, SKI, TCF12, TCOF1, TGFBR1, TGFBR2, TMCO1, TWIST1, WDR19, WDR35, ZIC1, ZSWIM6

    Test Information

    Test Method

    DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Utility

    Discrimination between multiple heritable disorders associated with craniofacial conditions; identification of causative mutations in complex cases that span multiple phenotypes; facilitation of targeted carrier testing of relatives of proband and/or predictive prenatal testing.

    Clinical Sensitivity

    The detection rate for the CraniofacialZoom panel is undetermined at this point, due to ongoing research in the field.

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

  • Number of Genes Included: 22
    Acceptable Sample Types:

    • Blood (3-6ml EDTA)
    • Saliva (Oragene 500 or 600)
    • Cultured Fibroblasts (T75 flask)
    • Extracted DNA (extracted from a CLIA-certified lab)

    Price: $2,915
    CPT Code: 81479
    Turnaround Time: 6-8 weeks
    Platform: Exome + del/dup analysis

    Genes: BRCA1, BRCA2, BRIP1, ERCC4, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, MAD2L2, PALB2, RAD51, RAD51C, RFWD3, SLX4, UBE2T, XRCC2

    Test Information

    Test Method

    DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Utility

    Discrimination between multiple heritable etiologies of Fanconi anemia; identification of causative mutations in complex cases that span multiple phenotypes; facilitation of targeted carrier testing of relatives of proband and/or predictive prenatal testing.

    Clinical Sensitivity

    The detection rate for the FancZoom panel is undetermined at this point, due to ongoing research in the field.

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

  • Number of Genes Included: 51
    Conditions Included: *Fragile bones
    *Osteopenia
    Acceptable Sample Types:

    • Blood (3-6ml EDTA)
    • Saliva (Oragene 500 or 600)
    • Cultured Fibroblasts (T75 flask)
    • Extracted DNA (extracted from a CLIA-certified lab)

    Price: $2,915
    CPT Code: 81479
    Turnaround Time: 6-8 weeks
    Platform: Exome + del/dup analysis

    Genes: ALPL, ANKH, ANO5, ATP6V0A2, B4GALT7, BMP1, CASR, CLCN5, COL1A1, COL1A2, CREB3L1, CRTAP, CYP27B1, DMP1, ENPP1, FGF23, FKBP10, GNAS, GORAB, IFIH1, IFITM5, LMNA, LRP5, MAFB, MMP2, NOTCH2, P3H1, P4HB, PHEX, PLOD2, PLS3, PPIB, PTH1R, PYCR1, RUNX2, SEC24D, SERPINF1, SERPINH1, SLC34A3, SP7, SPARC, TMEM38B, TNFRSF11A, TNFRSF11B  , TREM2, TRPV6, TYROBP, WNT1, XYLT2, ZMPSTE24

    Test Information

    Test Method

    DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Utility

    Discrimination between multiple heritable disorders associated with decreased bone mineral density; identification of causative mutations in complex cases that span multiple phenotypes; facilitation of targeted carrier testing of relatives of proband and/or predictive prenatal testing.

    Clinical Sensitivity

    The detection rate for the LowBoneDensityZoom panel is undetermined at this point, due to ongoing research in the field.

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

  • Number of Genes Included: 147
    Conditions Included

    • *Thrombocytopenia
    • *MDS and acute leukemia
    • *Short telomere syndromes
    • *Diamond-Blackfan anemia and DBA-like hypoplastic anemias
    • *Fanconi anemia
    • *Severe cogenital neutropenia
    • *Sideroblastic anemia
    • *Familial MPN
    • *Additional genes

    Acceptable Sample Types:

    • Blood (3-6ml EDTA)
    • Saliva (Oragene 500 or 600)
    • Cultured Fibroblasts (T75 flask)
    • Extracted DNA (extracted from a CLIA-certified lab)

    Price: $2,915
    CPT Code: 81479
    Turnaround Time: 6-8 weeks
    Platform: Exome + del/dup analysis

    Thrombocytopenia

    GenesACTN1, ANKRD26, CYCS, ETV6, FLI1, FLNA, FYB, GATA1, GATA2, GFI1B, GP1BA, GP1BB, GP9, HOXA11, ITGA2B, ITGB3, LYST, MPL, MYH9, NBEAL2, PRKACG, RBM8A, RUNX1, SLFN14, SRC, TUBB1, VWF, WAS

    Myelodysplastic syndrome and acute leukemia

    GenesANKRD26, CEBPA, DDX41, ETV6, GATA2, IKZF1, PAX5, RUNX1, SAMD9, SAMD9L, SRP72, TP53

    Familial MPN

    GenesJAK2, RBBP6, THPO

    Short telomere syndromes

    GenesACD, CTC1, DKC1, NAF1, NHP2, NOP10, PARN, POT1, RTEL1, STN1, TERC, TERT, TINF2, WRAP53, ZCCHC8

    Diamond-Blackfan Anemia and DBA-like hypoplastic anemias

    GenesCECR1, EPO, GATA1, MYSM1, RPL11, RPL15, RPL18, RPL26, RPL27, RPL31, RPL35, RPL35A, RPL5, RPS10, RPS15A, RPS17, RPS19, RPS24, RPS26, RPS27, RPS28, RPS29, RPS7, TSR2

    Fanconi anemia

    GenesBRCA1, BRCA2, BRIP1, ERCC4, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, MAD2L2, PALB2, RAD51, RAD51C, RFWD3, SLX4, UBE2T, XRCC2

    Severe congenital neutropenia

    GenesCSF3R, CXCR4, ELANE, G6PC3, GFI1, HAX1, JAGN1, TAZ, USB1, VPS45, WAS

    Sideroblastic anemia

    GenesABCB7, ALAS2, GLRX5, PUS1, SLC19A2, SLC25A38, TRNT1, YARS2

    Additional genesATM, BLM, C15ORF41, CBL, CHEK2, DNAJC21, EFL1, EPCAM, ERCC6L2, LIG4, LYST, MLH1, MPL, MSH2, MSH6, NBN, NF1, PMS2, PTPN11, RAB27A, RBM8A, SBDS, SLC19A2, SLC37A4, SRP54, VPS13B, YARS2

    Test Information

    Test Method

    DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Utility

    Discrimination between multiple heritable causes of bone marrow failure; identification of causative mutations in complex cases that span multiple phenotypes; facilitation of targeted carrier or presymptomatic testing of relatives of proband and/or predictive prenatal testing.

    Clinical Sensitivity

    The detection rate for the MarrowZoom panel is undetermined at this point, due to ongoing research in the field.

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

  • Number of Genes Included: 251
    Conditions Included

    • *Myopathy
    • *Charcot-Marie-Tooth
    • *Hereditary spastic paraplegia

    Acceptable Sample Types:

    • Blood (3-6ml EDTA)
    • Saliva (Oragene 500 or 600)
    • Cultured Fibroblasts (T75 flask)
    • Extracted DNA (extracted from a CLIA-certified lab)

    Price: $2,915
    CPT Code: 81479
    Turnaround Time: 6-8 weeks
    Platform: Exome + del/dup analysis

    Myopathy

    Genes: ACTA1, ADSS1, AGL, AGRN, ALG14, ALG2, AMPD1, ANO5, ASAH1, ATP2A1, B3GALNT2, B4GAT1, BAG3, BIN1, BVES, CACNA1S, CAPN1, CAPN3, CASQ1, CAV3, CAVIN1, CCDC78, CFL2, CHAT, CHKB, CHRNA1, CHRNB1, CHRND, CHRNE, CLCN1, CNTN1, COL12A1, COL13A1, COL6A1, COL6A2, COL6A3, COLQ, CPT2, CRPPA, CRYAB, DAG1, DCTN1, DES, DMD, DNAJB6, DNM2, DOK7, DPAGT1, DPM1, DPM2, DPM3, DYSF, EMD, FBXO38, FHL1, FKBP14, FKRP, FKTN, FLNC, GAA, GARS1, GBE1, GFPT1, GLE1, GMPPB, GNE, GYS1, HNRNPA1, HNRNPA2B1, HNRNPDL, ISCU, ITGA7, KBTBD13, KCNJ2, KLHL40, KLHL41, KY, LAMA2, LAMP2, LARGE1, LDB3, LIMS2, LMNA, LMOD3, LRP4, MATR3, MEGF10, MICU1, MTM1, MUSK, MYH2, MYH3, MYH7, MYO18B, MYOT, MYPN, NALCN, NEB, ORAI1, PAX7, PFKM, PLEC, PMM2, PNPLA2, POMGNT1, POMGNT2, POMK, POMT1, POMT2, PREPL, PYGM, PYROXD1, RAPSN, RXYLT1, RYR1, SCN4A, SELENON, SETX, SGCA, SGCB, SGCD, SGCE, SGCG, SIL1, SLC18A3, SLC52A2, SLC5A7, SNAP25, SPEG, SQSTM1, STAC3, STIM1, SYNE1, SYNE2, SYT2, TAZ, TCAP, TIA1, TMEM43, TNNI2, TNNT1, TNPO3, TOR1AIP1, TPM2, TPM3, TRAPPC11, TRIM32, TRIP4, TTN, UBA1, VCP, VMA21, VRK1

    Charcot-Marie-Tooth disease

    Genes: AARS1, AIFM1, ATL1, ATP7A, BICD2, BSCL2, DNAJB2, DNM2, DNMT1, DYNC1H1, EGR2, ELP1, FGD4, FIG4, GAN, GARS1, GDAP1, GJB1, GLA, GNB4, HARS1, HINT1, HSPB1, HSPB8, IGHMBP2, INF2, KIF1A, KIF5A, LITAF, LMNA, LRSAM1, MFN2, MME, MORC2, MPZ, MTMR2, NDRG1, NEFL, NGF, NTRK1, PHKA1, PLEKHG5, PMP22, PRDM12, PRPS1, PRX, RAB7A, REEP1, RETREG1, SBF1, SBF2, SCN11A, SCN9A, SEPTIN9, SH3TC2, SLC12A6, SLC52A2, SLC52A3, SPTLC1, SPTLC2, TFG, TRIM2, TRPV4, TTR, WNK1, YARS1

    Hereditary spastic paraplegia

    Genes: ABCD1, ALDH18A1, ALS2, AP4B1, AP4E1, AP4M1, AP4S1, AP5Z1, ATL1, ATP13A2, B4GALNT1, BSCL2, C12ORF65, CYP2U1, CYP7B1, DDHD1, DDHD2, ERLIN2, FA2H, GBA2, GJC2, HSPD1, KIF1A, KIF1C, KIF5A, L1CAM, NIPA1, NT5C2, PLP1, PNPLA6, REEP1, RTN2, SACS, SLC16A2, SLC33A1, SPART, SPAST, SPG11, SPG21, SPG7, TECPR2, TFG, VPS37A, WASHC5, ZFYVE26

    Test Information

    Test Method

    DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Utility

    Discrimination between multiple heritable disorders involving the neuromuscular system; identification of causative mutations in complex cases that span multiple phenotypes; facilitation of targeted carrier or presymptomatic testing of relatives of proband and/or predictive prenatal testing.

    Clinical Sensitivity

    The detection rate for the NeuromuscularZoom panel is undetermined at this point, due to ongoing research in the field.

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

  • Number of Genes Included: 106
    Conditions Included

    • *Mucociliary disorders
    • *Interstitial lung disease
    • *Pulmonary vascular disease

    Acceptable Sample Types:

    • Blood (3-6ml EDTA)
    • Saliva (Oragene 500 or 600)
    • Cultured Fibroblasts (T75 flask)
    • Extracted DNA (extracted from a CLIA-certified lab)

    Price: $2,915
    CPT Code: 81479
    Turnaround Time: 6-8 weeks
    Platform: Exome + del/dup analysis

    Mucociliary disorders

    Genes: ARMC4, CCDC103, CCDC114, CCDC151, CCDC39, CCDC40, CCDC65, CCNO, CFAP298, CFAP300, CFTR, DNAAF1, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAH1, DNAH11, DNAH5, DNAH8, DNAH9, DNAI1, DNAI2, DNAJB13, DNAL1, DRC1, FOXJ1, GAS2L2, GAS8, HYDIN, LRRC56, LRRC6, MCIDAS, NEK10, NME8, OFD1, PIH1D3, RPGR, RSPH1, RSPH3, RSPH4A, RSPH9, SCNN1A, SCNN1B, SCNN1G, SPAG1, SPZ1, TTC12, TTC25, ZMYND10

    Interstitial lung disease

    Genes: ABCA3, AP3B1, COPA, CSF2RA, CSF2RB, DKC1, ELMOD2, FLCN, FLNA, FOXF1, GATA2, GBA, HPS1, HPS4, IDUA, MARS, NAF1, NF1, NKX2-1, NPC2, OAS1, PARN, RAB5B, RTEL1, SFTPA1, SFTPA2, SFTPB, SFTPC, SLC34A2, SLC7A7, SMPD1, STAT3, TBX4, TERC, TERT, TINF2, TMEM173, TSC1, TSC2, ZCCHC8

    Pulmonary vascular disorders

    Genes: ABCC8, ACVRL1, ATP13A3, BMPR1B, BMPR2, CA12, CAV1, COL1A1, COL3A1, EIF2AK4, ENG, FBN1, FOXF1, GDF2, KCNA5, KCNK3, RASA1, SMAD9, TBX4

    Test Information

    Test Method

    DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Utility

    Discrimination between multiple heritable disorders that can cause diffuse lung disease; identification of causative variants in complex cases that span multiple phenotypes; facilitation of targeted carrier or presymptomatic testing of relatives of proband and/or predictive prenatal testing.

    Clinical Sensitivity

    The detection rate for the PulmZoom panel is undetermined at this point, due to ongoing research in the field.

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

  • Number of Genes Included: 338
    Conditions Included

    • *Glomerular diseasse and complement genes
    • *Disorders of ion transport, nephrolithiasis
    • *CAKUT, ciliopathies, tubulointerstitial disease, and other

    Acceptable Sample Types:

    • Blood (3-6ml EDTA)
    • Saliva (Oragene 500 or 600)
    • Cultured Fibroblasts (T75 flask)
    • Extracted DNA (extracted from a CLIA-certified lab)

    Price: $2,915
    CPT Code: 81479
    Turnaround Time: 6-8 weeks
    Platform: Exome + del/dup analysis

    Glomerular diseases and complement genes

    Genes: ACE, ACTN4, ADAMTS13, COQ8B, ALG1, ALMS1, ANLN, APOE, APOL1, AQP2, ARHGAP24, ARHGDIA, AVPR2, C1QA, C1QB, C1QC, C1R, C1S, C2, C2CD3, C3, C3AR1, C4A, C4B, C4BPA, C4BPB, C5, C5AR1, C6, C7, C8A, C8B, C8G, C9, CD151, CD2AP, CD46, CD55, CD59, CD93, CFB, CFD, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI, CFP, CLU, COL4A1, COL4A3, COL4A4, COL4A5, COL4A6, COQ2, COQ6, CR1, CR2, CRB2, CUBN, DGKE, ELANE, EMP2, ENPP1, F2, FAT1, FCN1, FCN2, FCN3, FGA, FN1, GLA, GLIS3, GREM1, HNF1B, HNF4A, INF2, ITGA3, ITGAM, ITGAX, ITGB2, ITGB4, LAMB2, LMX1B, MBL2, MEFV, MMACHC, MYH9, MYO1E, NPHS1, NPHS2, NUP107, NUP205, NUP93, OCRL, PAX2, PDSS2, PLCE1, PLCG2, PODXL, REN, SCARB2, SERPING1, SGPL1, SLC17A5, SLC5A1, SLC5A2, SMARCAL1, THBD, TNFRSF1A, TRPC6, VEGFA, VSIG4, VTN, WDR73, WT1

    Disorders of ion transport, nephrolithiasis, and nephrocalcinosis

    Genes: ACE, ADCY10, AGT, AGTR1, AGXT, APRT, AQP2, ATP6V0A4, ATP6V1B1, ATP7B, AVPR2, BSND, CACNA1D, CA2, CACNA1H, CACNA1S, CASR, CDC73, CLCN5, CLCNKA, CLCNKB, CLDN16, CLDN19, CNNM2, CUL3, CYP11B1, CYP11B2, CYP24A1, DMP1, EGF, EHHADH, ENPP1, FAH, FGF23, FXYD2, GATA3, GRHPR, HNF4A, HOGA1, HPRT1, HSD11B2, KCNJ1, KCNJ10, KCNJ2, KCNJ5, KLHL3, LRP5, MAGED2, NEDD4L, NOTCH2, NR3C2, OCRL, PHEX, PLG, REN, SARS2, SCN4A, SCNN1A, SCNN1B, SCNN1G, SLC12A1, SLC12A3, SLC22A12, SLC2A9, SLC34A1, SLC34A3, SLC3A1, SLC4A1, SLC4A4, SLC7A9, SLC9A3R1, TRPM6, VDR, WNK1, WNK4, XDH

    CAKUT, ciliopathies, tubulointerstitial diseases, and other

    Genes: ACE, COQ8A, AGT, AGTR1, AHI1, ALG9, ALMS1, ANKS6, APOA1, ARL13B, ARL6, B2M, B9D1, B9D2, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, BICC1, BMP4, BMPER, CPLANE1, C8orf37, CC2D2A, CDC73, CEP104, CEP120, CEP164, CEP290, CEP41, CEP83, CHD1L, CHD7, CLCN5, COLEC10, COLEC11, CREBBP, CSPP1, CTNS, DACH1, DCDC2, DHCR7, DHTKD1, DLC1, DLG1, DNAJB11, DSTYK, DYNC2H1, E2F3, EYA1, FAH, FAN1, FAT1, FGA, FGF20, FGFR1, FOXP1, FRAS1, FREM1, FREM2, GANAB, GATA3, GDNF, GLI3, GLIS2, GLIS3, GPC3, GRIP1, GSN, HNF1B, IFT122, IFT140, IFT172, IFT27, IFT43, IFT74, IFT80, INPP5E, INVS, IQCB1, ITGA8, ITGB2, JAG1, KCTD1, KIAA0556, KIAA0586, KIF12, KIF14, KIF7, LMNA, LRP5, LYZ, LZTFL1, MASP1, MASP2, MEFV, MKKS, MKS1, MUC1, NEIL1, NEK1, NEK8, NLRP3, NOTCH2, NPHP1, NPHP3, NPHP4, OFD1, PAX2, PBX1, PDE6D, PKD1, PKD2, PKHD1, PMM2, REN, RET, ROBO2, RPGRIP1L, SALL1, SALL4, SARS2, SDCCAG8, SEC61A1, SEMA3E, SIX1, SIX2, SIX5, SLC2A2, SLC41A1, SLIT2, SOX17, SRGAP1, TBX18, TCTN1, TCTN2, TCTN3, TFAP2A, TMEM107, TMEM138, TMEM216, TMEM231, TMEM237, TMEM67, TNXB, TRAP1, TRIM32, TSC1, TSC2, TTC21B, TTC8, TTR, UMOD, UPK3A, UPK3B, VHL, VIPAS39, VPS33B, WDPCP, WDR19, WDR35, WNT4, WT1, XPNPEP3, ZMPSTE24, ZNF423

    Test Information

    Test Method

    DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Utility

    Discrimination between multiple heritable etiologies of renal disease; identification of causative variants in complex cases that span multiple phenotypes; facilitation of targeted carrier or presymptomatic testing of relatives of proband and/or predictive prenatal testing.

    Clinical Sensitivity

    The detection rate for the RenalZoom panel is undetermined at this point, due to ongoing research in the field.

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

  • Number of Genes Included: 338
    Conditions Included

    • *Short-rib polydactyly
    • *Skeletal ciliopathies

    Acceptable Sample Types:

    • Blood (3-6ml EDTA)
    • Saliva (Oragene 500 or 600)
    • Cultured Fibroblasts (T75 flask)
    • Extracted DNA (extracted from a CLIA-certified lab)

    Price: $2,915
    CPT Code: 81479
    Turnaround Time: 6-8 weeks
    Platform: Exome + del/dup analysis

    Genes: CEP120, CSPP1, DYNC2H1, EVC, EVC2, FGFR1, FGFR2, FGFR3, IFT122, IFT140, IFT172, IFT80, KIAA0586, NEK1, PAPSS2, SLC26A2, SOX9, TCTN3, TTC21B, WDR19, WDR34, WDR35, WDR60

    Test Information

    Test Method

    DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Utility

    Discrimination between multiple heritable etiologies of short-rib polydactyly and skeletal ciliopathies; identification of causative mutations in complex cases that span multiple phenotypes; facilitation of targeted carrier testing of relatives of proband and/or predictive prenatal testing.

    Clinical Sensitivity

    The detection rate for the SkeletalZoom panel is undetermined at this point, due to ongoing research in the field.

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

  • Number of Genes Included: 10
    Conditions Included

    • *Stickler syndrome
    • *22q11 deletion syndrome

    Acceptable Sample Types:

    • Blood (3-6ml EDTA)
    • Saliva (Oragene 500 or 600)
    • Cultured Fibroblasts (T75 flask)
    • Extracted DNA (extracted from a CLIA-certified lab)

    Price: $2,915
    CPT Code: 81479
    Turnaround Time: 6-8 weeks
    Platform: Exome + del/dup analysis

    Genes: COL2A1, COL9A1, COL9A2, COL9A3, COL11A1, COL11A2, LOXL3, LRP2, VCAN

    (includes targeted analysis for 22q11 deletion)

    Test Information

    Test Method

    DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Utility

    Discrimination between multiple heritable etiologies of Stickler syndrome and 22q11 deletion syndrome; identification of causative mutations in complex cases that span multiple phenotypes; facilitation of targeted carrier testing of relatives of proband and/or predictive prenatal testing.

    Clinical Sensitivity

    The detection rate for the Skeletal22qZoom panel is undetermined at this point, due to ongoing research in the field.

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

  • Number of Genes Included: 15

    Acceptable Sample Types:

    • Blood (3-6ml EDTA)
    • Saliva (Oragene 500 or 600)
    • Cultured Fibroblasts (T75 flask)
    • Extracted DNA (extracted from a CLIA-certified lab)

    Price: $2,915
    CPT Code: 81479
    Turnaround Time: 6-8 weeks
    Platform: Exome + del/dup analysis

    Genes: ACD; CTC1; DKC1; NAF1; NHP2; NOP10; PARN; POT1; RTEL1; STN1; TERC; TERT; TINF2; WRAP53; ZCCHC8

    *Please note that TeloZoom is an exome-based test. If you need Telomere Length Testing, please contact Molecular Diagnostics Lab at molecularpathresults@jhmi.edu and 410-955-1438.

    Telomere Length Testing Requisition Form              DDL Test Requisition Forms

    Syndrome Information

    Clinical Description

    Short telomere syndromes are a spectrum of disease phenotypes that result from variants in genes involved in telomere maintenance PMID 22965356. The most common clinical manifestations are listed here and they may co-occur in patients and affected families.

    Idiopathic pulmonary fibrosis is an age-related disorder characterized by scarring of the lungs. It runs in families and ~20% of idiopathic pulmonary fibrosis patients have an affected first degree relative PMID 22079513. Other types of lung disease cluster in families with germline defects in telomere maintenance including non-specific interstitial pneumonitis, pleuroparenchymal fibroelastosis (PPFE), chronic hypersensitivity pneumonitis and emphysema PMID 17392301PMID 29703687PMID 25562321.

    Liver disease may be a first manifestation of short telomere syndromes either as cirrhosis or hepatopulmonary syndrome PMID 19936245PMID 26158642.

    Bone marrow failure includes spectrum of failed hematopoiesis and includes isolated cytopenias, overt aplastic anemia as well as myelodysplastic syndrome.

    Immunodeficiency may also be a manifestation of primary short telomere syndromes alone or in combination with bone marrow failure PMID 30179220. Hoyeraal-Hreidarsson syndrome (HHS) is a severe short telomere syndrome that is classically associated with immunodeficiency, colitis PMID 23279657, intrauterine growth restriction, microcephaly, and cerebellar hypoplasia.

    Dyskeratosis congenita is a classic short telomere disorder characterized by characteristic mucocutaneous findings namely nail dystrophy, oral leukoplakia and skin hyperpigmentation. Revesz syndrome is a rare bilateral exudative retinopathy which has been seen in pediatric patients with short telomere syndromes including Hoyeraal-Hreidarsson syndrome.

    Coats plus syndrome is rare and has distinguishing features from other short telomere syndromes such as intracranial calcifications. It is most commonly caused by biallelic variants in CTC1 PMID 22267198.

    Inheritance Pattern

    Autosomal dominant, autosomal recessive, X-linked recessive, and de novo

    Genotype-Phenotype Correlation

    Telomere length is the strongest predictor of disease phenotype as well as severity in this group of disorders PMID 29463756. Genetic anticipation may show evolving patterns of disease in autosomal dominant families with older generations affected by pulmonary disease and younger generations by bone marrow failure PMID 21436073. Some clinical phenotypes that have genotype correlations additionally include:

    • Hoyeraal-Hreidarsson syndrome is commonly caused by mutations in DKC1 or TINF2 but has also been reported with biallelic variants in TERT, RTEL1 and PARN PMID 25940403.
    • Revesz syndrome is often associated with variants in TINF2 PMID 18252230.
    • Biallelic variants in CTC1 usually manifest as Coats plus syndrome (intracranial calcifications, retinal exudates, osteopenia, gastrointestinal bleeding). CTC1 biallelic variants may also be seen in rare cases of isolated bone marrow failure PMID 22532422.

    Reversion has been described in patients with TERC variants PMID 22341970 and in one adult with a TINF2 variant PMID 25539146. If a patient who meets diagnostic criteria for short telomere syndrome has a negative molecular testing, it might be beneficial to repeat the sequencing from a non-hematopoietic tissue (e.g. fibroblast).

    Test Information

    Test Method

    DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Utility

    Discrimination of genetic causes of short telomere disorders; identification of causative variants in known or highly suspicious cases; facilitation of targeted testing of relatives of probands and/or predictive or prenatal testing.

    Clinical Sensitivity

    Variants in telomerase and telomere maintenance genes manifest in a number of clinical presentations that span infancy to adulthood. Testing telomere length by flow cytometry and FISH can functionally identify some of these patients and may also predictive of the severity of disease PMID 21436073. Approximately, 30% of patients with familial forms of pulmonary fibrosis and telomere-related lung disease carry variants in telomerase and telomere maintenance PMID 25539146. In sporadic cases of idiopathic pulmonary fibrosis, an estimated 5% of patients carry a variant. For unselected patients with idiopathic pulmonary fibrosis (i.e. a mix of familial and sporadic disease) approximately 10% carry germline variants in the common telomere maintenance genes PMID 28099038. For patients with familial clustering of bone marrow failure and idiopathic pulmonary fibrosis, approximately 80% carry variants in telomere maintenance genes PMID 21436073. Variants in telomere-related genes are likely the most common cause of inherited forms of bone marrow failure PMID 29146883. Telomere-mediated disease may also more rarely manifest as classic dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome or other more rare phenotypes as aforementioned where the yield of identifying the short telomere defect by flowFISH (link) is high and for identifying a disease-causing variant up to 80%.

    Telomere length testing by flowFISH is offered through the Johns Hopkins Molecular Diagnostics Laboratory.

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

    Other testing relevant to the valuation of inherited pulmonary fibrosis: PulmZoom

    Sample Requirements

    3-6ml whole blood in EDTA (purple topped) tubes
    Saliva collected in an appropriate collection device (Oragene®-DNA 500 or 600 device)
    DNA extracted from fibroblast or lymphocyte cell line (must be extracted in a CLIA-certified laboratory)

    Turn Around Time

    Approximately 6-8 weeks

    Fee and CPT Codes

    Exome Panel: $2915
    CPT Code: 81479
    *If you are a provider outside of Johns Hopkins we are only accepting institutional billing

    Helpful Links

  • Genes: N/A

    Test Information

    Test Method: Clinical Exome Sequencing Test

    Special Considerations

    If you receive a negative Zoom report, but still suspect a diagnosis of a genetic condition in your patient, the ZoomOut test can be your next step, where all the protein-coding genes in the genome will be analyzed.

    Helpful Links

Exome 

Price: $5,600 to $7,850

  • Genes: N/A

    Test Information

    Test Method

    DNA extraction (if applicable) and ultrasonic fragmentation; targeted capture of the coding regions and intron/exon boundaries of protein coding RefSeq genes using a TWIST custom exome library capture; next generation sequencing (NGS) on an Illumina NovaSeq instrument; alignment to the human reference genome (GRCh37/hg19) using the Burrows-Wheeler Aligner (bwa); variant calling using GATK and detection of exonic deletions and duplications using ExomeDepth; Sanger sequencing to confirm low quality and/or complex indel variants related to the specified phenotype(s); Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Sensitivity

    The clinical sensitivity of this assay is dependent on the phenotypic information provided to the laboratory. A causative genetic variant is identified in approximately 20-30% of affected individuals (Farwell et al., 2015, PMID 25356970; Retterer et al., 2016, PMID 26633542; Yang et al., 2013, PMID 24088041). Variants in the ACMG list of secondary findings genes are identified in approximately 1-4% of individuals (Kalia, et al., 2017, PMID 27854360; Olfson et al., 2015, PMID 26332594; Schwarz, et al., 2018, PMID 30100086). This test is only validated for inherited gene alterations associated with the specified phenotype(s).

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

    Sample Requirements

    3-6ml whole blood in EDTA (purple topped) tubes
    Saliva collected in an appropriate collection device (Oragene®-DNA 500 or 600 device)
    DNA extracted from fibroblast or lymphocyte cell line (must be extracted in a CLIA-certified laboratory)

    Turn Around Time: Approximately 6-8 weeks

    Fee and CPT Codes

    Exome Proband-Only: $5600
    Exome Duo: $6350
    Exome Trio: $7100
    Exome Quad: $7850

    CPT Code: 81415 and 81416
    *If you are a provider outside of Johns Hopkins we are only accepting institutional billing

    Helpful Links

  • Genes: N/A

    Test Information

    Test Method

    Review of sequence and dosage data for the specified genes by multiple staff members; Variant classification following ACMG criteria (if applicable). Bioinformatic analysis was performed using DDL pipeline DDL.TWISTExome.v1.2020_12_22 and DDL.TWIST.Exome.Dosage.v1.2020_12_20.

    Clinical Sensitivity

    The clinical sensitivity of this assay is dependent on the phenotypic information provided to the laboratory. A causative genetic variant is identified in approximately 20-30% of affected individuals (Farwell et al., 2015, PMID 25356970; Retterer et al., 2016, PMID 26633542; Yang et al., 2013, PMID 24088041). Variants in the ACMG list of secondary findings genes are identified in approximately 1-4% of individuals (Kalia, et al., 2017, PMID 27854360; Olfson et al., 2015, PMID 26332594; Schwarz, et al., 2018, PMID 30100086). This test is only validated for inherited gene alterations associated with the specified phenotype(s).

    Analytic Sensitivity

    Sequencing: >94% for single nucleotide and >76% for small insertion/deletion variants for the nucleotides evaluated. Exonic deletions/duplications: >97% for unique regions of the genome. This test is not validated to identify small deletions/insertions of greater than 20bp, exonic deletions and duplications in pseudogenes or other repetitive regions of the genome (e.g. segmental duplications), nucleotide repeat expansions, mitochondrial DNA variants or mosaicism. Disease-associated variants in regions that are not captured and/or sufficiently sequenced will not be detected by this assay.

    Sample Requirements: N/A - Analysis-Only

    Turn Around Time: 3-4 weeks

    Fee and CPT Codes: 81479

    Helpful Links

Targeted

  • Genes: HTT

    Acceptable Sample Types

    Blood (3-6ml EDTA)
    Saliva (Oragene 500 or 600)
    Cultured Fibroblasts (T75 flask)
    Extracted DNA (extracted from a CLIA-certified lab)
    Contact lab for information about prenatal testing

    Platform: Repeat sizing

    Syndrome Information

    Clinical Description

    Huntington Disease (HD) features progressive motor, cognitive and psychiatric disturbances.  Patients may experience clumsiness, balance and gait disturbances as well as other issues with both voluntary and involuntary movement, dysarthria, oculomotor disturbances, weakness, weight loss, personality changes, and depression.  Age of onset is usually in the 4th decade. 

    Patients with Juvenile HD have a similar set of symptoms, but experience a more rapid decline.  Motor and cerebellar symptoms are prominent.  Onset is usually before age 20.  Seizures occur in cases with onset before age 10.

    Inheritance Pattern: Autosomal Dominant

    Genotype-Phenotype Correlation

    Repeat length is associated with age at symptom onset (Juvenile HD versus classic HD), faster progression of disease, and decreased variability in age at symptom onset.

    Reduced penetrance alleles are described.   

    Test Information

    Test Method

    PCR and fragment sizing of the CAG repeat region of the HTT gene

    Clinical Utility

    Identification of causative mutations in known or highly suspicious cases of a Huntington Disease; Rule-out HD in the presence of equivocal clinical presentation; Predictive testing in relatives of a proband with an HTT mutation.

    Clinical Sensitivity

    Of patients meeting clinical diagnostic criteria for Huntington Disease, 98-99% will have an expanded CAG repeat in exon 1 of the HTT gene.  Reduced penetrance (60% by age 65 and 70% by age 75) has been identified in individuals with expansions from  36 to 39 CAG repeats.

    Analytic Sensitivity

    The repeat size provided in the report is +/- 1 CAG repeat up to 40; +/- 2 CAG repeats 41-60; and, +/- 3 CAG repeats when >60 repeats.  The assay may not detect expansions larger than 101 repeats. 

    Sample Requirements

    3-6ml whole blood in EDTA (purple topped) tubes. (see Pediatric or Adult blood sample algorithms for additional information)

    We prefer whole blood for all tests.

    Turn Around Time: 2-3 weeks

    Fee and CPT Codes

    $355 for routine testing on a blood sample
    CPT Code:  81271

    Please contact the lab to arrange testing for relatives of a proband or prenatal samples.  

    Special Considerations

    The Huntington Disease Society has guidelines for presymptomatic testing for Huntington Disease (HD) (and similar adult-onset neurodegenerative conditions) that outline a team approach over several in-person sessions.  These guidelines are summarized in our Presymptomatic HD checklist (sections 5, 8, and 9 for counseling recommendations).

    INFORMED CONSENT from the patient is required prior to ordering a genetic test. The DNA Diagnostic Lab's consent is located on the second page of the requisition form

    Helpful Links

  • Genes: JPH3

    Acceptable Sample Types

    Blood (3-6ml EDTA)
    Saliva (Oragene 500 or 600)
    Cultured Fibroblasts (T75 flask)
    Extracted DNA (extracted from a CLIA-certified lab)
    Contact lab for information about prenatal testing

    Syndrome Information

    Clinical Description

    Huntington Disease-like 2 (HDL2) is clinically similar to Juvenile onset Huntington Disease.  Patients experience adult onset (usually by the 4th decade) of symptoms that include progressive movement disorder (parkinsonism, chorea), cognitive and emotional decline (dementia, psychiatric disturbances). Unlike Juvenile onset HD, seizures and eye movement abnormalities are usually not described. Some cases may follow a pattern of symptom onset more like classic Huntington Disease. 

    Inheritance Pattern: Autosomal Dominant

    Genotype-Phenotype Correlation

    None; known intra- and inter-familial variability; Reduced penetrance expansion alleles have been described.

    Test Information

    Test Method

    PCR and fragment sizing of the CAG/CTG repeat region of the JPH3 gene

    Clinical Utility

    Identification of causative mutations in known or highly suspicious cases of a Huntington Disease-like phenotype, especially when HD testing is negative; Rule-out HDL2 in the presence of equivocal clinical presentation; Predictive testing in relatives of a proband with a JPH3 mutation.

    Clinical Sensitivity

    HDL2 is a rare disorder and the clinical significance of some repeat lengths is still being characterized.  Of Black African patients with symptoms of Huntington Disease who tested negative for HTT expansions, approximately 35% will have expansions of the JPH3 gene consistent with HDL2.   In North Americans, 3/374 patient (<1%) with symptoms of Huntington Disease had JPH3 expansions.  The penetrance of this disorder is not known.  

    Analytic Sensitivity

    The repeat size provided in the report is +/- 1 CAG/CTG repeat up to 40; +/- 2 CAG/CTG repeats 41-60; and, +/- 3 CAG/CTG repeats when >60 repeats.  The assay may not detect expansions larger than 101 repeats. 

    Sample Requirements

    3-6ml whole blood in EDTA (purple topped) tubes. (see Pediatric or Adult blood sample algorithms for additional information)

    We prefer whole blood for all tests.

    Turn Around Time: 2-3 weeks

    Fee: $437 for routine testing on a blood sample
    CPT Code:  81479

    Please contact the lab to arrange testing for relatives of a proband or prenatal samples.  

    Special Considerations

    The Huntington Disease Society has guidelines for presymptomatic testing for Huntington Disease (HD) (and similar adult-onset neurodegenerative conditions) that outline a team approach over several in-person sessions.  These guidelines are summarized in our Presymptomatic HD checklist (sections 5, 8, and 9 for counseling recommendations).

    INFORMED CONSENT from the patient is required prior to ordering a genetic test. The DNA Diagnostic Lab's consent is located on the second page of the requisition form

    Helpful Links

  • Number of Genes Included: Please provide report listing targeted variant information

    Acceptable Sample Types

    Blood (3-6ml EDTA)
    Saliva (Oragene 500 or 600)
    Cultured Fibroblasts (T75 flask)
    Extracted DNA (extracted from a CLIA-certified lab)

    Price: $400
    CPT Code: 81403
    Turnaround Time: 3 weeks
    Platform: Sanger

  • Number of Genes Included: Please provide report listing targeted variant information

    Acceptable Sample Types

    Direct Villi (10mg, cleaned)
    Cultured Villi (2 T25 flasks)
    Cultured Amniocytes (2 T25 flasks)
    Extracted DNA (extracted from a CLIA-certified lab)
    Cord Blood
    Maternal Sample required

    Price: $1,350
    CPT Code: 81479
    Turnaround Time: 3 weeks
    Platform: Sanger

  • Number of Genes Included: Please provide report listing targeted variant information

    Acceptable Sample Types

    Direct Villi (10mg, cleaned)
    Cultured Villi (2 T25 flasks)
    Cultured Amniocytes (2 T25 flasks)
    Extracted DNA (extracted from a CLIA-certified lab)
    Cord Blood
    Maternal Sample required

    Price: $600
    CPT Code: 81265
    Turnaround Time: 1 week
    Platform: Fragment Analysis

 
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