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

Abstract

Oral–facial–digital syndrome type 1 (OFD1) is a male-lethal X-linked dominant disorder characterized by a dysmorphic face, associated with oral cavity and digital anomalies. Polycystic kidney disease is another typical feature of this syndrome. Heterozygous mutations in the OFD1 gene are responsible for this condition. This gene encodes a centrosomal and basal body cilia protein that plays an important role in the early development of the brain, face, limbs and kidneys. In this study we clinically evaluated an affected Emirati female child exhibiting features of OFD1 syndrome. Screening of the OFD1 gene was carried out using a Sanger DNA sequencing method. Moreover, bioinformatics tools were used to predict the pathogenicity of the identified mutation. As a result, we identified a heterozygous single-nucleotide deletion in the donor splice site of exon 20 (c.2757+1delG). Both parents were homozygous for the wild-type alleles. The deletion might be a de novo mutation in nature, but we cannot exclude the possibility of mosaicism in the mother. Prediction analyses showed that the deletion abolishes the authentic splice site leading to the generation of a cryptic splice site. Subsequently, this mutation will result in a frameshift and premature termination codon (p.Lys920ArgfsX2). In this report, we describe the clinical features and molecular studies of an Emirati child with OFD1 syndrome. To our knowledge this is the first report of the clinical and molecular aspect of OFD1 from the UAE.