|DNA Diagnostic Laboratory at Johns Hopkins|
Treacher Collins Syndrome
POLR1D; chr13q12.2 (TCS2)
POLR1C; chr6p21.1 (TCS3)
Treacher Collins Syndrome (TCS) primarily affects craniofacial
development. The most common features include
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
Dominant (TCOF1, POLR1D); Autosomal Recessive (POLR1C);
Variable expressivity and non-penetrance have been reported
None known; reported TCS caused by POLR1D and POLR1C mutations is clinically indistinguishable from that caused by TCOF1 mutations
sequencing of the coding regions and intron-exon boundaries of
TCOF1 multiplex ligation-dependent probe amplification (MLPA) for deletions
(Must be ordered as separate tests - see Special Considerations below for suggested test strategy)
|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.|
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
Approximately 2-4% of
patients with Treacher Collins Syndrome will have a TCOF1
deletion. Deletions comprise approximately 5% of TCOF1 mutations.
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 95%.
|Turn Around Time:||
TCOF1 sequence: 3-4 weeks
POLR1D sequence: 3-4 weeks
POLR1C sequence: 3-4 weeks
TCOF1 MLPA: 4 weeks
|Fee and CPT Codes:||
TCOF1 sequence: $2630 for
TCOF1 MLPA: $429 for routine
POLR1D sequence: $470 for routine testing
sequence: $1086 for routine testing
|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.|
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.