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

Ahmed K Shalaby, Peter Emery-Billcliff, Diana Baralle, Tabib Dabir, Shahiba Begum, Sarah Waller, Lydia Tabernero, Martin Lowe, James Self

Journal: Molecular vision 2019;24():847-852

PMID: 30713423

Free Full Text on Molecular Vision View on PubMed

Abstract

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 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 gene can present as apparently isolated congenital cataract.

Address: Ophthalmology Department, Princess of Wales Hospital, Manchester, UK.; School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.; Human Development and Health, University of Southampton, UK.; Northern Regional Genetics Service Belfast City Hospital, Molecular Diagnostics and Microbiology, Belfast UK.; Royal Stoke Hospital, Stoke-on-Trent, UK.; Genomic Diagnostics Laboratory, Manchester Centre for Genomic Medicine, Manchester, UK.; Clinical and Experimental Sciences, University of Southampton, UK.

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MeSH Terms: Amino Acid Substitution, Binding Sites, Cataract, Child, Gene Expression, Hemizygote, Humans, Male, Oculocerebrorenal Syndrome, Pedigree, Phenotype, Phosphoric Monoester Hydrolases, Point Mutation, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Folding, Protein Interaction Domains and Motifs, rab GTP-Binding Proteins