Department of Biological Sciences, Faculty of Basic and Applied Sciences, International Islamic University, H-10, Islamabad, 44000, Pakistan.
Faculty of Basic and Applied Sciences, SA-Centre for Interdisciplinary Research in Basic Sciences, International Islamic University, H-10, Islamabad, 44000, Pakistan.
BMC Ophthalmol. 2024 Aug 14;24(1):345. doi: 10.1186/s12886-024-03611-6.
Oculocutaneous albinism (OCA) is a genetically heterogeneous condition that is associated with reduced or absent melanin pigment in the skin, hair, and eyes, resulting in reduced vision, high sensitivity to light, and rapid and uncontrolled eye movements. To date, seventeen genes have been associated with OCA including syndromic and non-syndromic forms of the condition.
Whole exome sequencing (WES) was performed to identify pathogenic variants in nine Pakistani families with OCA, with validation and segregation of candidate variants performed using Sanger sequencing. Furthermore, the pathogenicity of the identified variants was assessed using various in-silico tools and 3D protein structural analysis software.
WES identified biallelic variants in three genes explaining the OCA in these families, including four variants in TYR, three in OCA2, and two in HPS1, including two novel variants c.667C > T: p.(Gln223*) in TYR, and c.2009 T > C: p.(Leu670Pro) in HPS1.
Overall, this study adds further knowledge of the genetic basis of OCA in Pakistani communities and facilitates improved management and counselling services for families suffering from severe genetic diseases in Pakistan.
眼皮肤白化病（OCA）是一种遗传异质性疾病，其特征是皮肤、头发和眼睛中的黑色素减少或缺失，导致视力下降、对光敏感以及眼球快速且不受控制的运动。迄今为止，已有十七个基因与 OCA 相关，包括该病症的综合征和非综合征形式。
对九个有 OCA 的巴基斯坦家庭进行全外显子组测序（WES），以鉴定致病性变异，使用 Sanger 测序对候选变异进行验证和分离。此外，使用各种计算工具和 3D 蛋白质结构分析软件评估鉴定出的变异的致病性。
WES 在三个基因中鉴定出了导致这些家庭 OCA 的双等位基因变异，包括 TYR 中的四个变异、OCA2 中的三个变异和 HPS1 中的两个变异，包括两个新的变异 c.667C>T:p.(Gln223*)在 TYR 中，以及 c.2009T>C:p.(Leu670Pro)在 HPS1 中。
总的来说，这项研究进一步了解了巴基斯坦人群中 OCA 的遗传基础，并为巴基斯坦严重遗传疾病患者的家庭提供了更好的管理和咨询服务。
