Identification and functional analysis of a novel oculocerebrorenal syndrome of Lowe (OCRL) gene variant in two pedigrees with varying phenotypes including isolated congenital cataract

PURPOSE: To identify the genetic variation in two unrelated probands with congenital cataract and to perform functional analysis of the detected variants. METHODS: Clinical examination and phenotyping, segregation, and functional analysis were performed for the two studied pedigrees. RESULTS: A novel OCRL gene variant (c.1964A>T, p. (Asp655Val)) was identified. This variant causes defects in OCRL protein folding and mislocalization to the cytoplasm. In addition, the variant’s location close to the Rab binding site is likely to be associated with membrane targeting abnormalities. CONCLUSIONS: The results highlight the importance of early genetic diagnosis in infants with congenital cataract and show that mutations in the OCRL gene can present as apparently isolated congenital cataract.