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

• Published in: Npj genomic medicine Vol. 6; no. 1; p. 14
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-02-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/212/2301; 631/208/2489/144; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Case Report; Gene Function; Gene Therapy; Genetic disorders; Human Genetics; Internal Medicine; Mutation; Bangladesh
• ISSN: 2056-7944; 2056-7944
• 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.