A novel CEP78 variant and rod-cone dystrophy in non-consanguineous siblings

INTRODUCTION: To report a case of two siblings with a novel CEP78 mutation, presenting with Rod-Cone Dystrophy (RCD). METHODS: This is an observational case report of two Chinese male siblings, born to non-consanguineous parents, presenting with severe rod-cone dystrophy seen on clinical examination, multimodal imaging, and electroretinogram. Both patients underwent targeted gene sequencing. The parents of both patients underwent targeted gene sequencing of requested variants to determine inheritance. RESULTS: Patient 1 and 2 presented with symptoms of RCD at ages 7 and 42 years old respectively. Clinical examination, as well as imaging and electroretinogram findings were consistent with the diagnosis of RCD. Both patients were found to harbour compound heterozygous variants in the CEP78 gene, a novel loss of function mutation c.1288_1291dup (p.Pro431Glnfs *6) and a missense mutation classified as a Variant of Unknown Significance (VUS) c.830T>C (p.Leu277Pro). CONCLUSIONS: This report describes two siblings with RCD due to compound heterozygous variants in the CEP78 gene; one novel, the other currently classified as VUS. The data presented herein support the latter being reclassified as pathogenic.