A ‘de novo’ splice site deletion in the OFD1 gene is responsible for oral–facial–digital type 1 syndrome in an Emirati child

Abstract

Introduction: Oral– facial– digital type 1 (OFD1) syndrome is an X-linked dominant disease characterized by dysmorphic face, oral cavity and digits. This syndrome is associated with polycystic kidney disease, which is a typical feature of OFD1. Heterozygous mutations in the OFD1 gene are responsible for this condition. This gene encodes acentrosomal and basal body cilia proteins that play an important role in the early development of the brain, face, limbs and the kidneys. Objectives: In this study we clinically evaluated an Emirati female exhibiting OFD1 syndrome features. Material and methods: Screening of the OFD1 gene was carried out using Sanger DNA sequencing. Moreover, bioinformatics tools have been used to predict the pathogenicity of the identified mutation. Results: We identified a heterozygous single-nucleotide deletion in the donor splice site of exon 20 (c.2757+1delG). Since both parents were homozygous for the wild-type alleles, we concluded that the deletion is a ‘de novo’ mutation. Prediction analyses showed that the deletion abolishes the authentic splice site leading to the generation of a cryptic splice site, resulting in a frame-shift mutation and premature termination codon (p.Lys920ArgfsX2). Conclusions: We described the clinical features and molecular studies of a sporadic case of an Emirati female with OFD1 syndrome. Acknowledgements: Professor Bassam Ali for supervising the project.