| DNA Diagnostic Laboratory at Johns Hopkins |  |
| DNA Diagnostic Laboratory at Johns Hopkins | |
Treacher Collins Syndrome |
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| Genes: |
TCOF1;
chr5q32 (TCS1) POLR1D; chr13q12.2 (TCS2) POLR1C; chr6p21.1 (TCS3) |
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| Syndrome Information | ||
| Clinical Description: |
Treacher Collins Syndrome (TCS) primarily affects craniofacial
development. The most common features include
downward slanting
palpebral fissures and lower lid coloboma; hypoplasia of malar bones and
micrognathia; dysmorphic or hypoplastic external ears; and atresia of
middle-ear ossicles sometimes resulting in conductive hearing loss.
Cleft palate and unilateral or bilateral choanal atresia are also
possible. |
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| Inheritance Pattern: | Autosomal
Dominant (TCOF1, POLR1D); Autosomal Recessive (POLR1C);
Variable expressivity and non-penetrance have been reported |
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| Genotype-Phenotype Correlation: | None known; reported TCS caused by POLR1D and POLR1C mutations is clinically indistinguishable from that caused by TCOF1 mutations |
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| Test Information | ||
| Test Method: | Bidirectional
sequencing of the coding regions and intron-exon boundaries of TCOF1 POLR1D and/or POLR1C TCOF1 multiplex ligation-dependent probe amplification (MLPA) for deletions (Must be ordered as separate tests - see Special Considerations below for suggested test strategy) |
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| Clinical Utility: | Identification of causative mutations in known or highly suspicious cases of Treacher Collins Syndrome; assessment of recurrence risk within the family; targeted diagnostic testing of relatives of proband with inconclusive clinical presentations; predictive prenatal testing when familial mutation is known. | |
| Clinical Sensitivity: |
TCOF1 sequence:
78-93%
of patients with a clinical diagnosis of Treacher Collins Syndrome are
expected top have a point mutation in TCOF1. POLR1D sequence: Approximately 7% of TCOF1 negative patients are expected to have POLR1D mutations. POLR1C sequence: Approximately 1% of TCOF1 negative patients are expected to have POLR1C mutations TCOF1 MLPA: There are no published
cases of Treacher Collins Syndrome caused by large TCOF1 deletions,
although this would be compatible with the proposed mutation mechanism of
haploinsufficiency. During the course of development and validation,
we identified a patient with a multiple exon deletion. |
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Analytic Sensitivity: |
Sequence: Greater
than 97% for nucleotides analyzed. All reports will indicate if a
certain percentage of
nucleotides were not called or were analyzed in a single direction. MLPA: Estimated to be at least 90%. |
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| Turn Around Time: |
TCOF1 sequence: 3-4 weeks POLR1D sequence: 3-4 weeks POLR1C sequence: 3-4 weeks TCOF1 MLPA: 4 weeks |
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| Fee and CPT Codes: |
TCOF1 sequence: $2630 for
routine testing on a blood sample 83891 x 1; 83898 x 26; 83904 x 52; 83909 x 52; 83912 x 1
TCOF1 MLPA: $429 for routine
testing on a blood or DNA sample POLR1D sequence: $470 for routine testing on a blood or
DNA sample POLR1C
sequence: $1086 for routine testing on a blood or DNA sample
Please contact the lab to arrange testing for known mutations on blood or prenatal samples. |
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| Special Considerations | ||
| TCOF1 point mutations account for the majority of TCS cases, and sequencing should be ordered as a first-tier test. POLR1D and POLR1C are ordered ideally as second-tier tests after TCOF1. POLR1D and POLR1C may be considered in sporadic cases. POLR1D testing should be considered if there is a family history of Treacher Collins Syndrome in multiple generations. POLR1C testing should be considered in families with multiple affected siblings or with consanguinity. These these tests may be ordered in any combination or order desired by the referrer. Please add comments about test order or reflexing in the Notes/Clinical Information section of the requisition form (page 2) or speak with laboratory staff to arrange testing prior to shipping the sample. | ||
| 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. There is also a patient brochure, "Things Every Patient Should Know Before Consenting to a Genetic Test", available for download. | ||
Helpful Links |
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| Sample Requirements Requisition and Billing forms Clinical information on Treacher Collins Syndrome Link to the General Test Information page for a discussion of the uses and limitations of genetic testing Patient and Family Page for general resources on genetic testing. |
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