A Novel Pathogenic Splicing Mutation of OFD1 is Responsible for a Boy with Joubert Syndrome Exhibiting Orofaciodigital Spectrum Anomalies, Polydactyly and Retinitis Pigmentosa

Joubert syndrome (JS) is an infrequent congenital neurodevelopmental ciliopathy, typically identified in children around the average age of 33 months. This disorder is characterized by developmental delay, cognitive impairment, and infantile hypotonia that may evolve into ataxia. Mutations in <i>OFD1</i> results in Joubert syndrome with a variety of phenotypes. Here, we identified a child who presented with Joubert syndrome exhibiting orofaciodigital spectrum anomalies, polydactyly, and retinitis pigmentosa. Whole exome sequencing and Sanger sequencing revealed a splicing mutation (NM_003611.2, c.2387+1G>A) in the <i>OFD1</i> gene of the patient and his mother. mRNA sequencing further confirmed this mutation. However, since the patient is homozygous and the mother is heterozygous, only the patient has the phenotype and the mother is normal. This mutation can lead to the loss of sixth coiled-coil domains of OFD1 protein, which further disrupt the ciliary signaling pathway and Hedgehog signaling pathway. This study presents a new case of JS and expands the mutant spectrum of <i>OFD1</i>, but also enhances our understanding of the mechanism by which <i>OFD1</i> is associated with ciliosis.