Genetic Causes of Oculocutaneous Albinism in Pakistani Population
Waryah, Yar M
Mughal, Tauqeer A
Rao, Ali R
Abbasi, Ansar A
Shaikh, Rehan S
Waryah, Ali M
Ahmed, Zubair M
MetadataShow full item record
AbstractMelanin pigment helps protect our body from broad wavelength solar radiation and skin cancer. Among other pigmentation disorders in humans, albinism is reported to manifest in both syndromic and nonsyndromic forms as well as with varying inheritance patterns. Oculocutaneous albinism (OCA), an autosomal recessive nonsyndromic form of albinism, presents as partial to complete loss of melanin in the skin, hair, and iris. OCA has been known to be caused by pathogenic variants in seven different genes, so far, according to all the currently published population studies. However, the detection rate of alleles causing OCA varies from 50% to 90%. One of the significant challenges of uncovering the pathological variant underlying disease etiology is inter- and intra-familial locus heterogeneity. This problem is especially pertinent in highly inbred populations. As examples of such familial locus heterogeneity, we present nine consanguineous Pakistani families with segregating OCA due to variants in one or two different known albinism-associated genes. All of the identified variants are predicted to be pathogenic, which was corroborated by several in silico algorithms and association with diverse clinical phenotypes. We report an individual affected with OCA carries heterozygous, likely pathogenic variants in TYR and OCA2, raising the question of a possible digenic inheritance. Altogether, our study highlights the significance of exome sequencing for the complete genetic diagnosis of inbred families and provides the ramifications of potential genetic interaction and digenic inheritance of variants in the TYR and OCA2 genes.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/15437
- Genetic studies of multiple consanguineous Pakistani families segregating oculocutaneous albinism identified novel and reported mutations.
- Authors: Gul H, Shah AH, Harripaul R, Mikhailov A, Prajapati K, Khan E, Ullah F, Zubair M, Ali MZ, Shah AH, Salman S, Khan S, Vincent JB, Khan MA
- Issue date: 2019 Jul
- Molecular genetic studies and delineation of the oculocutaneous albinism phenotype in the Pakistani population.
- Authors: Jaworek TJ, Kausar T, Bell SM, Tariq N, Maqsood MI, Sohail A, Ali M, Iqbal F, Rasool S, Riazuddin S, Shaikh RS, Ahmed ZM
- Issue date: 2012 Jun 26
- Screening of TYR, OCA2, GPR143, and MC1R in patients with congenital nystagmus, macular hypoplasia, and fundus hypopigmentation indicating albinism.
- Authors: Preising MN, Forster H, Gonser M, Lorenz B
- Issue date: 2011 Apr 15
- Ophthalmo-genetic analysis of Pakistani patients with nonsyndromic oculocutaneous albinism through whole exome sequencing.
- Authors: Gul H, Ali MZ, Khan E, Zubair M, Badar M, Khan S, Shah AH, Khan MA
- Issue date: 2017 May
- Mutational Analysis of the TYR and OCA2 Genes in Four Chinese Families with Oculocutaneous Albinism.
- Authors: Wang Y, Wang Z, Chen M, Fan N, Yang J, Liu L, Wang Y, Liu X
- Issue date: 2015