Whole exome sequencing uncovered highly penetrant recessive mutations for a spectrum of rare genetic pediatric diseases in Bangladesh
Autor: | Mazharul Islam, Ghausia Begum, Tahrima Arman Tusty, Nushrat Jahan Dity, Shaoli Sarkar, Marc Woodbury-Smith, Hosneara Akter, Md. Atikur Rahaman, Mohammed Uddin, Bakhrom K. Berdeiv, Reem Abdel Hameid, Mohammad Basiruzzaman, K. M. Furkan Uddin, Sharmin Jahan, Darren D. O’Rielly, Elaine T. Lim, Mohammed Nazmul Ahsan, A.H.M. Nurun Nabi, Stephen W. Scherer, Mohammad Shahnoor Hossain, Dimitri J. Stavropoulos, Nasna Nassir, Muhammad Sougatul Islam |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Population Case Report 030105 genetics & heredity Biology QH426-470 Compound heterozygosity XY gonadal dysgenesis 03 medical and health sciences symbols.namesake medicine Genetics education Molecular Biology Gene Genetics (clinical) Exome sequencing Sanger sequencing education.field_of_study Genetic heterogeneity Mucolipidosis Disease genetics medicine.disease 030104 developmental biology symbols Medicine Medical genomics |
Zdroj: | npj Genomic Medicine, Vol 6, Iss 1, Pp 1-9 (2021) NPJ Genomic Medicine |
ISSN: | 2056-7944 |
Popis: | 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: | OpenAIRE |
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