Whole exome sequencing uncovered highly penetrant recessive mutations for a spectrum of rare genetic pediatric diseases in Bangladesh.

Abstract

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.

• Authors: Hosneara Akter, Mohammad Shahnoor Hossain, Nushrat Jahan Dity, Md Atikur Rahaman, K M Furkan Uddin, Nasna Nassir, Ghausia Begum, Reem Abdel Hameid, Muhammad Sougatul Islam, Tahrima Arman Tusty, Mohammad Basiruzzaman, Shaoli Sarkar, Mazharul Islam, Sharmin Jahan, Elaine T Lim, Marc Woodbury-Smith, Dimitri James Stavropoulos, Darren D O'Rielly, Bakhrom K Berdeiv, A H M Nurun Nabi, Mohammed Nazmul Ahsan, Stephen W Scherer, Mohammed Uddin
• Journal: NPJ genomic medicine (NPJ Genom Med) Vol. 6 Issue 1 Pg. 14 (Feb 16 2021) ISSN: 2056-7944 [Electronic] England
• PMID: 33594065 (Publication Type: Journal Article)