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Genes: COL2A1, COL9A1, COL9A2, COL9A3, COL11A1, COL11A2, LOXL3, LRP2, VCAN, TBX1

(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 the Agilent Clinical Research Exome kit; next generation sequencing (NGS) on an Illumina HiSeq 2500 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; targeted analysis for 22q11 deletion;  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.CRExome.v1.2019_07_15 and DDL.CRExome.Dosage.v1.2019_08_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

> 99% for single nucleotide and >92% for small insertion/deletion variants for the nucleotides evaluated. Lower limit of detection: Single nucleotide variants: 25% allele frequency (>96% sensitivity), Small insertion/deletion variants: 50% allele frequency (>94% sensitivity). This test is not validated to identify deletions/insertions of greater than 20bp, copy number changes, 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

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