|DNA Diagnostic Laboratory at Johns Hopkins|
Treacher Collins Syndrome
|Genes:||TCOF1; chr5q32 (TCS1)||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
|Genotype-Phenotype Correlation:||None known; reported TCS caused by POLR1D and POLR1C mutations is clinically indistinguishable from that caused by TCOF1 mutations|
Generation Sequencing (NGS) and/or Sanger sequencing of the coding regions and intron-exon boundaries of
the listed genes; Automatically reflexed to TCOF1 deletion/duplication testing by MLPA analysis if
|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 to have a point mutation in TCOF1, depending on diagnostic
stringency. Of TCOF1 negative patients, approximately
7% are expected to have POLR1D mutations and
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.
>99% accuracy for inherited single nucleotide and small
insertion/deletion variants for the nucleotides evaluated.
analysis parameters are not designed to assess mosaicism.
Del/Dup: Greater than 99% for MLPA probes analyzed.
|Turn Around Time:||
Sequence: Approximately 4 weeks
TCOF1 MLPA: up to 4 weeks
|Fee and CPT Codes:||Sequence:
TCOF1 MLPA: $429 for routine
|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
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.