Akter Hosneara, Hossain Mohammad Shahnoor, Dity Nushrat Jahan, Rahaman Md Atikur, Furkan Uddin K M, Nassir Nasna, Begum Ghausia, Hameid Reem Abdel, Islam Muhammad Sougatul, Tusty Tahrima Arman, Basiruzzaman Mohammad, Sarkar Shaoli, Islam Mazharul, Jahan Sharmin, Lim Elaine T, Woodbury-Smith Marc, Stavropoulos Dimitri James, O'Rielly Darren D, Berdeiv Bakhrom K, Nurun Nabi A H M, Ahsan Mohammed Nazmul, Scherer Stephen W, Uddin Mohammed
Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh.
Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.
NPJ Genom Med. 2021 Feb 16;6(1):14. doi: 10.1038/s41525-021-00173-0.
Collectively, rare genetic diseases affect a significant number of individuals worldwide. In this study, we have conducted whole-exome sequencing (WES) and identified underlying pathogenic or likely pathogenic variants in five children with rare genetic diseases. We present evidence for disease-causing autosomal recessive variants in a range of disease-associated genes such as DHH-associated 46,XY gonadal dysgenesis (GD) or 46,XY sex reversal 7, GNPTAB-associated mucolipidosis II alpha/beta (ML II), BBS1-associated Bardet-Biedl Syndrome (BBS), SURF1-associated Leigh Syndrome (LS) and AP4B1-associated spastic paraplegia-47 (SPG47) in unrelated affected members from Bangladesh. Our analysis pipeline detected three homozygous mutations, including a novel c. 863 G > C (p.Pro288Arg) variant in DHH, and two compound heterozygous variants, including two novel variants: c.2972dupT (p.Met991Ilefs*) in GNPTAB and c.229 G > C (p.Gly77Arg) in SURF1. All mutations were validated by Sanger sequencing. Collectively, this study adds to the genetic heterogeneity of rare genetic diseases and is the first report elucidating the genetic profile of (consanguineous and nonconsanguineous) rare genetic diseases in the Bangladesh population.
总体而言，罕见遗传病影响着全球大量个体。在本研究中，我们对五名患有罕见遗传病的儿童进行了全外显子组测序（WES），并鉴定出潜在的致病或可能致病的变异。我们提供了一系列疾病相关基因中致病常染色体隐性变异的证据，这些基因包括与DHH相关的46,XY性腺发育不全（GD）或46,XY性反转7、与GNPTAB相关的黏脂贮积症II型α/β（ML II）、与BBS1相关的巴德-比埃尔综合征（BBS）、与SURF1相关的 Leigh综合征（LS）以及与AP4B1相关的痉挛性截瘫47（SPG47），这些变异存在于来自孟加拉国的无血缘关系的患病个体中。我们的分析流程检测到三个纯合突变，包括DHH基因中一个新的c.863 G > C（p.Pro288Arg）变异，以及两个复合杂合变异，包括两个新变异：GNPTAB基因中的c.2972dupT（p.Met991Ilefs*）和SURF1基因中的c.229 G > C（p.Gly77Arg）。所有突变均通过桑格测序进行了验证。总体而言，本研究增加了罕见遗传病的遗传异质性，并且是第一份阐明孟加拉国人群（近亲通婚和非近亲通婚）罕见遗传病基因图谱的报告。
