一个大型巴基斯坦队列中遗传性视网膜疾病的综合遗传图谱。
A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort.
作者信息
Ullah Mukhtar, Rehman Atta Ur, Quinodoz Mathieu, Rashid Abdur, Cancellieri Francesca, Munir Asad, Kaminska Karolina, Iqbal Afia, Javed Samra, Dawood Muhammad, Baig Hafiz Muhammad Azhar, Saleha Shamim, Naz Shagufta, Kausar Humera, Waryah Ali Muhammad, Superti-Furga Andrea, Ansar Muhammad, Rivolta Carlo
机构信息
Ophthalmic Genetics, Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
Department of Ophthalmology, University of Basel, Basel, Switzerland.
出版信息
NPJ Genom Med. 2025 Apr 4;10(1):31. doi: 10.1038/s41525-025-00488-2.
Inherited retinal diseases (IRDs) are a group of rare Mendelian disorders that often result in progressive vision loss and potentially to complete blindness at the end stage. In this study, we investigated a large cohort of patients with IRDs from Pakistan, the world's fifth most populous country, which is also characterized by distinctive demographic features, such as a high prevalence of consanguinity, endogamy, and a wide variety of ethnic groups. Specifically, we examined a total of 213 unrelated families (722 affected individuals) from three very large geographical regions. We achieved precise molecular diagnosis in 171 pedigrees (80.3%) and detected causative variants in 60 different IRD-associated genes, revealing a mutational landscape that differed substantially from previous data from other European or Asian populations, heavily shaped by endogamy and rare or recurrent founder mutational events. To our knowledge, this work represents the largest genetic study on IRDs within the Pakistani population.
遗传性视网膜疾病(IRDs)是一组罕见的孟德尔疾病,通常会导致进行性视力丧失,并在疾病终末期可能导致完全失明。在本研究中,我们调查了来自世界第五人口大国巴基斯坦的一大群IRD患者,该国还具有独特的人口特征,例如近亲结婚、族内通婚的高发生率以及各种各样的种族群体。具体而言,我们检查了来自三个非常大的地理区域的总共213个无亲缘关系的家庭(722名受影响个体)。我们在171个家系(80.3%)中实现了精确的分子诊断,并在60个不同的IRD相关基因中检测到致病变异,揭示了一个与先前来自其他欧洲或亚洲人群的数据有很大差异的突变格局,这主要由族内通婚以及罕见或反复出现的奠基者突变事件所塑造。据我们所知,这项工作代表了巴基斯坦人群中关于IRD的最大规模基因研究。