Whole exome sequencing reveals a homozygous SGCB variant in a Pakhtun family with limb girdle muscular dystrophy (LGMDR4) phenotype

Tariq, M., Latif, M., Inam, M., Jan, A., Bibi, N., Mohamoud, H. S. A., Ali, I., Ahmad, H., Khan, A., Nasir, J., Wadood, A. and Jelani, M. (2021) Whole exome sequencing reveals a homozygous SGCB variant in a Pakhtun family with limb girdle muscular dystrophy (LGMDR4) phenotype. Gene Reports. 22 2452-0144.

2020_Tariq_Muhammad_etal_Elsevier_Whole_exome_sequencing_reveals_a_homozygous_SGCB_variant_in_a_Pakhtun_fa ... (356kB)

Item Type:	Article
Abstract:	Limb-girdle muscular dystrophy (LGMD) is a term used for proximal muscles weakness mainly affecting arms, shoulders, legs and thighs. These patients have altered body posture due to weak muscles, and have difficulty in holding, standing or walking. Genetic causes of both autosomal dominant (LGMDD/LGMD1) and recessive (LGMDR/LGMD2) forms have been identified. We analyzed a consanguineous Pakhtun family from Khyber Pakhtunkhwa (KP), Pakistan. The disease started at early childhood (7–8 years). The phenotype worsened, and the patients had become completely wheelchair bound in teenages. Whole exome sequencing (WES) at 100× coverage on Illumina NovaSeq6000 platform followed by Sanger sequencing revealed a homozygous variant (c.610T > C; p.Ser204Pro) in the SGCB gene known for LGMDR4 phenotype. Structural protein prediction tools and molecular docking analyses showed critical structural changes in the binding interface and SGCB protein tunnel. To the best of our knowledge this is the first report of SGCB variant identified in a Pakistani family. Structural analysis of p.Ser204Pro substitution gives insight into SGCB pathogenicity causing LGMDR4 phenotype. WES analysis can be used as a first line tool in rare diseases molecular diagnostics. Encouraging premarital testing in the closest relatives of such patients may have positive impact on reduction of the recurrence risk in their subsequent generations.
Uncontrolled Keywords:	LGMDR4, Pakhtun family, Protein modeling, Sarcoglycan beta gene, Whole exome sequencing
Creators:	Tariq, Muhammad, Latif, Muhammad, Inam, Memona, Jan, Amin, Bibi, Nousheen, Mohamoud, Hussein Sheikh Ali, Ali, Isse, Ahmad, Habib, Khan, Aziz, Nasir, Jamal, Wadood, Abdul and Jelani, Musharraf
Faculties, Divisions and Institutes:	?? ASSCI ??
Date:	March 2021
Date Type:	Publication
Journal or Publication Title:	Gene Reports
Volume:	22
Language:	English
DOI:	https://doi.org/10.1016/j.genrep.2020.101014
ISSN:	2452-0144
Status:	Published / Disseminated
Refereed:	Yes
Related URLs:	https://www.mendeley.com/catalogue/b7c83... https://pure.northampton.ac.uk/en/public...
URI:	http://nectar.northampton.ac.uk/id/eprint/15701

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