Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort

GNE gene-specific c.2179G>A(p.V727M) is a key alteration reported in patients with hereditary inclusion body myopathy (HIBM) and represents an ethnic founder mutation in the Indian cohort. However, the underlying role of this mutation in pathogenesis remains largely unknown. Thus, in this study,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Attri Shivangi, Sharma Vikas, Kumar Amit, Verma Chaitenya, Gahlawat Suresh Kumar
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2021
Materias:	hibm gne myopathy simulation founder mutations Medicine R
Acceso en línea:	https://doaj.org/article/3551ad28983a4a1ab38e7f374d695949
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3551ad28983a4a1ab38e7f374d695949
record_format	dspace
spelling	oai:doaj.org-article:3551ad28983a4a1ab38e7f374d6959492021-12-05T14:10:55ZDissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort2391-546310.1515/med-2021-0391https://doaj.org/article/3551ad28983a4a1ab38e7f374d6959492021-11-01T00:00:00Zhttps://doi.org/10.1515/med-2021-0391https://doaj.org/toc/2391-5463GNE gene-specific c.2179G>A(p.V727M) is a key alteration reported in patients with hereditary inclusion body myopathy (HIBM) and represents an ethnic founder mutation in the Indian cohort. However, the underlying role of this mutation in pathogenesis remains largely unknown. Thus, in this study, we aimed to access possible mechanisms of V727M mutation that could be leading to myopathy. We evaluated various in silico tools to predict the effect of this mutation on pathogenicity, structural or possible interactions, that could induce myopathy. Our results propose that V727M mutation could induce deleterious effects or pathogenicity and affect the stability of GNE protein. Analysis of differential genes reported in the V727 mutant case suggests that it can affect GNE protein interaction with Myc-proto-oncogene (MYC) transcription factor. Our in silico analysis also suggests a possible interaction between GNE ManNac-kinase domain with MYC protein at the C-terminal DNA-binding domain. MYC targets reported in skeletal muscles via ChIP-seq suggest that it plays a key role in regulating the expression of many genes reported differentially expressed in V727M-mutated HIBMs. We conclude that V727M mutation could alter the interaction of GNE with MYC thereby altering transcription of sialyltransferase and neuromuscular genes, thus understanding these effects could pave the way for developing effective therapies against HIBM.Attri ShivangiSharma VikasKumar AmitVerma ChaitenyaGahlawat Suresh KumarDe Gruyterarticlehibmgnemyopathysimulationfounder mutationsMedicineRENOpen Medicine, Vol 16, Iss 1, Pp 1733-1744 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hibm gne myopathy simulation founder mutations Medicine R
spellingShingle	hibm gne myopathy simulation founder mutations Medicine R Attri Shivangi Sharma Vikas Kumar Amit Verma Chaitenya Gahlawat Suresh Kumar Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
description	GNE gene-specific c.2179G>A(p.V727M) is a key alteration reported in patients with hereditary inclusion body myopathy (HIBM) and represents an ethnic founder mutation in the Indian cohort. However, the underlying role of this mutation in pathogenesis remains largely unknown. Thus, in this study, we aimed to access possible mechanisms of V727M mutation that could be leading to myopathy. We evaluated various in silico tools to predict the effect of this mutation on pathogenicity, structural or possible interactions, that could induce myopathy. Our results propose that V727M mutation could induce deleterious effects or pathogenicity and affect the stability of GNE protein. Analysis of differential genes reported in the V727 mutant case suggests that it can affect GNE protein interaction with Myc-proto-oncogene (MYC) transcription factor. Our in silico analysis also suggests a possible interaction between GNE ManNac-kinase domain with MYC protein at the C-terminal DNA-binding domain. MYC targets reported in skeletal muscles via ChIP-seq suggest that it plays a key role in regulating the expression of many genes reported differentially expressed in V727M-mutated HIBMs. We conclude that V727M mutation could alter the interaction of GNE with MYC thereby altering transcription of sialyltransferase and neuromuscular genes, thus understanding these effects could pave the way for developing effective therapies against HIBM.
format	article
author	Attri Shivangi Sharma Vikas Kumar Amit Verma Chaitenya Gahlawat Suresh Kumar
author_facet	Attri Shivangi Sharma Vikas Kumar Amit Verma Chaitenya Gahlawat Suresh Kumar
author_sort	Attri Shivangi
title	Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
title_short	Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
title_full	Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
title_fullStr	Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
title_full_unstemmed	Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
title_sort	dissecting role of founder mutation p.v727m in gne in indian hibm cohort
publisher	De Gruyter
publishDate	2021
url	https://doaj.org/article/3551ad28983a4a1ab38e7f374d695949
work_keys_str_mv	AT attrishivangi dissectingroleoffoundermutationpv727mingneinindianhibmcohort AT sharmavikas dissectingroleoffoundermutationpv727mingneinindianhibmcohort AT kumaramit dissectingroleoffoundermutationpv727mingneinindianhibmcohort AT vermachaitenya dissectingroleoffoundermutationpv727mingneinindianhibmcohort AT gahlawatsureshkumar dissectingroleoffoundermutationpv727mingneinindianhibmcohort
_version_	1718371595879186432

Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort

Ejemplares similares