Treacher Collins syndrome: a clinical and molecular study based on a large series of patients.
Genet Med
; 18(1): 49-56, 2016 Jan.
Article
in En
| MEDLINE
| ID: mdl-25790162
ABSTRACT
PURPOSE:
Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS,TCOF1, POLR1D, and POLR1C.METHODS:
We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene.RESULTS:
We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature.CONCLUSION:
Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphoproteins
/
DNA-Directed RNA Polymerases
/
Nuclear Proteins
/
Mandibulofacial Dysostosis
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Genet Med
Journal subject:
GENETICA MEDICA
Year:
2016
Document type:
Article
Affiliation country:
Francia