Functional characterization of two novel splicing mutations in the OCA2 gene associated with oculocutaneous albinism type II

Gene
Valeria RimoldiPaola Primignani

Abstract

Oculocutaneous albinism (OCA) is characterized by hypopigmentation of the skin, hair and eye, and by ophthalmologic abnormalities caused by a deficiency in melanin biosynthesis. OCA type II (OCA2) is one of the four commonly-recognized forms of albinism, and is determined by mutation in the OCA2 gene. In the present study, we investigated the molecular basis of OCA2 in two siblings and one unrelated patient. The mutational screening of the OCA2 gene identified two hitherto-unknown putative splicing mutations. The first one (c.1503+5G>A), identified in an Italian proband and her affected sibling, lies in the consensus sequence of the donor splice site of OCA2 intron 14 (IVS14+5G>A), in compound heterozygosity with a frameshift mutation, c.1450_1451insCTGCCCTGACA, which is predicted to determine the premature termination of the polypeptide chain (p.I484Tfs*19). In-silico prediction of the effect of the IVS14+5G>A mutation on splicing showed a score reduction for the mutant splice site and indicated the possible activation of a newly-created deep-intronic acceptor splice site. The second mutation is a synonymous transition (c.2139G>A, p.K713K) involving the last nucleotide of exon 20. This mutation was found in a young African alb...Continue Reading

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Citations

Aug 1, 2014·Human Molecular Genetics·Elvezia M ParaboschiRosanna Asselta
Dec 17, 2014·ELife·Nicholas W BellonoElena Oancea
Aug 5, 2016·Journal of Human Genetics·Letizia StranieroStefano Duga
Oct 14, 2016·Journal of Human Genetics·Lucia MauriPaola Primignani
Feb 14, 2018·Genetic Testing and Molecular Biomarkers·Biyuan QiuJiyun Yang
Feb 4, 2021·Scientific Reports·Abdullah AamirMervyn G Thomas

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