Mutation Analysis of a Pakistani Oculocutaneous Albinism Family Identifies a Novel Splice Site Defect in OCA2 Gene

Oculocutaneous albinism (OCA) is a multi-systemic and rare genetic disorder of pigmentation. It occurs due to defects in the melanin synthesis pathway. OCA is characterized by hypopigmentation of hair, dermis, and ocular tissue. The clinical consequences of OCA includes whitish skin, whitish to gold...

Full description

Saved in:
Bibliographic Details
Published inPakistan journal of zoology Vol. 54; no. 3; p. 1215
Main Authors Gul, Hadia, Shah, Abdul haleem, harripaul, Ricardo, Mikhailov, Anna, Khan, Ejaz Ullah, Shah, Wasim, Ahmad, Nisar, Vincent, John B, Khan, Muzammil Ahmad
Format Journal Article
LanguageEnglish
Published Lahore Knowledge Bylanes 30.06.2022
AsiaNet Pakistan (Pvt) Ltd
Subjects
Albinism
Causes of
Chromosome 15
Data analysis
Dermis
DNA microarrays
Gene mapping
Gene mutations
Genes
Genetic analysis
Genetic aspects
Genetic disorders
Genetic research
Genomes
Genomics
Genotyping
Hair
Homozygosity
Human population genetics
Mapping
Melanin
mRNA
Mutation
Nucleotides
Pigmentation
Proteins
White people
Pakistan
Online AccessGet full text

Cover

More Information
Summary:Oculocutaneous albinism (OCA) is a multi-systemic and rare genetic disorder of pigmentation. It occurs due to defects in the melanin synthesis pathway. OCA is characterized by hypopigmentation of hair, dermis, and ocular tissue. The clinical consequences of OCA includes whitish skin, whitish to golden hair and photophobia. Genetic studies have so far reported seven non-syndromic OCA genes, among which Pakistani OCA families mostly segregate TYR and OCA2 gene mutations. In the present study we aimed to investigate the genetic factor of OCA in a consanguineous family from Pakistan. Genetic analysis was performed through microarray genotyping and homozygosity-by-descent (hBD) mapping, whole exome sequencing (for mutation identification) and Sanger sequencing (for variant segregation). homozygosity analysis revealed a 1.2 Mb hBD region on chromosome 15 between markers rs4778147 to rs8036234 (chr15:27752745-28962131bp), which harbors the previously reported OCA2 gene. The subsequent whole exome sequencing identified a novel splice site defect at spice donor site, wherein G was replaced by T at genomic position 28171268 (NM000275.2:c.2079+5G>T) within intron-19 of the OCA2 gene. This change presumably may either includes few intronic nucleotides or skip exon-20 in the mature mRNA. Our study further supports the evidence of high incidence of OCA2 gene mutations in Pakistani families. Keywords: Oculocutaneous albinism, OCA2, homozygosity-by-descent mapping, Whole exome sequencing, Splice site defect
ISSN:0030-9923
0030-9923
DOI:10.17582/journal.pjz/20200501060515