Faily S, Perveen R, Urquhart J, Clayton-Smith J..
The University of Manchester and the Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, St Mary`s Hospital. | | Background | | Oral-facial-digital syndromes (OFDS) are a group of rare genetic disorders that are associated with congenital anomalies of the oral cavity, face and digits together with multi-systemic manifestations. To date 13 different OFDS have been classified, each characterised by their unique phenotypic spectrum of clinical features and patterns of inheritance. Oral-facial-digital (OFD) syndrome type 1 (OFD1) accounts for the vast majority of cases, it is an established ciliopathy and is associated with mutations in the OFD1 gene. | | | | Materials/methods | | We investigated patients with clinical features compatible with an OFD syndrome phenotype where the genetic basis was unknown, aiming to identify genetic variants in genes encoding ciliopathy proteins. Eleven patients from eight unrelated families were recruited onto the study. For each affected case, their clinical phenotype was accurately defined in comprehensive case reports. A variety of techniques for genomic analysis were employed, such as candidate gene analysis using Sanger sequencing, array comparative genomic hybridization, homozygosity mapping and whole exome sequencing. | | | | Results | | Our study further delineated the phenotypic spectrum of OFDS. We discovered a novel pathogenic heterozygous missense mutation c.635G>C (p.Arg212Pro) in the OFD1 gene in one family and an OFD1 deletion in a second. A novel pathogenic homozygous substitution mutation c.1859G>T (p.*620Leuext*22) was identified in the known OFD syndrome type 5 gene Dead-box polypeptide 59 gene (DDX59) in a two further affected patients from unrelated families. | | | | Conclusion | | : Molecular diagnostic confirmation has been achieved in five patients from four families. This has implications for medical management and will help to deliver optimal patient care. The variants discovered broaden the spectrum of known mutations. OFDS syndromes are confirmed as clinically and genetically heterogeneous disorders with genes identified affecting ciliary development and function. | | |
DOI No: https://doi.org/10.7199/ped.oncall.2016.5S
| Cite this article as: | | S F, R P, J U, J. C. A Clinical and Molecular Genetic Study of Oral-facial-digital Syndromes.. Pediatr Oncall J. 2016;13. doi: 10.7199/ped.oncall.2016.5S |
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