Abstract
Oculocutaneous albinism (OCA) is associated with a wide range of clinical presentations and has been categorized with syndromic and non-syndromic features. The most common causative genes in non-syndromic OCA are TYR and OCA2 and HSP1 is in the syndromic albinism. The objective of this study was to identify pathogenic variants in congenital OCA families from Pakistan. Eight consanguineous families were recruited, and clinical and ophthalmological examination was carried out to diagnose the disease. Whole blood was collected from the participating individuals, and genomic DNA was extracted for sequencing analysis. TruSight one-panel sequencing was carried out on one affected individual of each family, and termination Sanger sequencing was carried out to establish the co-segregation of the causative gene or genes. In silico analysis was conducted to predict the causative pathogenic variants. Two families were found to have novel genetic pathogenic variants, and six families harbored previously reported variants. One novel compound heterozygous pathogenic variant in the TYR gene, c.1002delA; p.Ala335LeufsTer20, a novel frameshift deletion pathogenic variant and c.832C>T; and p.Arg278Ter (a known pathogenic variant) were found in one family, whereas HPS1; c.437G>A; and p.Trp146Ter were detected in another family. The identification of new and previous pathogenic variants in TYR, OCA2, and HPS1 genes are causative of congenital OCA, and these findings are expanding the heterogeneity of OCA.
Highlights
Albinism is a rare genetic disorder arising from the impairment of melanin biosynthesis
More than 400 pathogenic variants have been identified in TYR, and more than 300 pathogenic variants are associated with OCA2
Pathogenic variants of TYR, OCA2, and Hermansky–Pudlak Syndrome 1 (HPS1) genes were detected in Oculocutaneous albinism (OCA) families of Pakistani origin
Summary
Albinism is a rare genetic disorder arising from the impairment of melanin biosynthesis It is categorized into ocular albinism, which influences only the eyes; and oculocutaneous albinism, which involves the skin, eyes, and hair. The clinical presentations of OCA are variable in each subtype These features include nystagmus, photophobia, hypopigmentation of skin, hair and eyes, mild to moderate reduced visual acuity, and iridis trans-illumination [2–4]. Eighteen OCA-associated genes have been reported in syndromic and non-syndromic phenotypes. Out of these genes, seven genes/loci are linked to autosomal recessive nsOCA. Seven genes/loci are linked to autosomal recessive nsOCA These genes include TYR, OCA2, TYRP1, SLC45A2, SLC24A5, C10orf, and DCT [1–4]. In Pakistani families, OCA1 is the most common OCA type, followed by OCA2 [1,2,8,9]
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