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

Autor:	Akter H; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh.; Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh., Hossain MS; Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh., Dity NJ; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh., Rahaman MA; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh., Furkan Uddin KM; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh., Nassir N; College of Medicine, Mohammed Bin Rashid University of Medicine and Health Science, Dubai, UAE., Begum G; College of Medicine, Mohammed Bin Rashid University of Medicine and Health Science, Dubai, UAE., Hameid RA; College of Medicine, Mohammed Bin Rashid University of Medicine and Health Science, Dubai, UAE., Islam MS; BioTED, Dhaka, Bangladesh., Tusty TA; Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh., Basiruzzaman M; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh.; Department of Child Neurology, NeuroGen Children's Healthcare, Dhaka, Bangladesh., Sarkar S; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh.; Department of Child Neurology, NeuroGen Children's Healthcare, Dhaka, Bangladesh., Islam M; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh.; Department of Child Neurology, NeuroGen Children's Healthcare, Dhaka, Bangladesh., Jahan S; Department of Endocrinology & Metabolism, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh., Lim ET; Department of Genetics, Harvard Medical School, Boston, USA., Woodbury-Smith M; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada.; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK., Stavropoulos DJ; Genome Diagnostics, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada., O'Rielly DD; Faculty of Medicine, Memorial University, St. John's, NL, Canada., Berdeiv BK; College of Medicine, Mohammed Bin Rashid University of Medicine and Health Science, Dubai, UAE., Nurun Nabi AHM; Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh., Ahsan MN; Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh., Scherer SW; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada.; McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., Uddin M; College of Medicine, Mohammed Bin Rashid University of Medicine and Health Science, Dubai, UAE. mohammed.uddin@mbru.ac.ae.
Jazyk:	angličtina
Zdroj:	NPJ genomic medicine [NPJ Genom Med] 2021 Feb 16; Vol. 6 (1), pp. 14. Date of Electronic Publication: 2021 Feb 16.
DOI:	10.1038/s41525-021-00173-0
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu