Spectrum of Clinical Variability with SEPT9 Gene Mutation in Hereditary Neuralgic Amyotrophy: Understanding the Pathogenesis Using Molecular Dynamics Simulation Study.
Journal
Neurology India
ISSN: 1998-4022
Titre abrégé: Neurol India
Pays: India
ID NLM: 0042005
Informations de publication
Date de publication:
01 Sep 2024
01 Sep 2024
Historique:
received:
12
10
2019
accepted:
18
08
2020
medline:
21
10
2024
pubmed:
21
10
2024
entrez:
21
10
2024
Statut:
ppublish
Résumé
Hereditary Neuralgic Amyotrophy (HNA) is an autosomal dominant disorder characterized by episodes of severe pain and amyotrophy affecting the brachial plexus as well as other sites. Mutations in the SEPTIN9 gene have been identified as genetic abnormality for HNA. Although the genetic mutations are known, their pathogenesis for the causation of this disorder is not exactly elucidated. In this study, we have investigated the phenotypic and genetic features in a large pedigree with HNA. We report the clinical spectrum and genetic analysis of a family with 9 affected members. Clinical heterogeneity has been reported in the individuals having mutations in SEPTIN9 gene. After taking informed consent, we have done genetic analysis of 6 affected and 4 unaffected members of the family to identify the molecular abnormalities of SEPTIN9 gene. Genetic analysis has identified the presence of NM_001113491.2:p.Arg106Trp mutation in SEPTIN9 gene. The same mutation has been identified in 6 affected members of the family. Molecular simulation study has revealed that the mutation has significantly altered the conformation of septin-9 protein, thereby impairing the microtubule binding and bundling ability. Although the affected members shared a common recurrent mutation, they have a wide spectrum of clinical variability. This may be due to the variable penetrance of the mutation and different epigenetic influences in the family. This is the first genetically confirmed case series of HNA reported from India.
Sections du résumé
BACKGROUND
BACKGROUND
Hereditary Neuralgic Amyotrophy (HNA) is an autosomal dominant disorder characterized by episodes of severe pain and amyotrophy affecting the brachial plexus as well as other sites. Mutations in the SEPTIN9 gene have been identified as genetic abnormality for HNA. Although the genetic mutations are known, their pathogenesis for the causation of this disorder is not exactly elucidated.
OBJECTIVE
OBJECTIVE
In this study, we have investigated the phenotypic and genetic features in a large pedigree with HNA.
METHODS
METHODS
We report the clinical spectrum and genetic analysis of a family with 9 affected members. Clinical heterogeneity has been reported in the individuals having mutations in SEPTIN9 gene. After taking informed consent, we have done genetic analysis of 6 affected and 4 unaffected members of the family to identify the molecular abnormalities of SEPTIN9 gene.
RESULTS AND CONCLUSIONS
CONCLUSIONS
Genetic analysis has identified the presence of NM_001113491.2:p.Arg106Trp mutation in SEPTIN9 gene. The same mutation has been identified in 6 affected members of the family. Molecular simulation study has revealed that the mutation has significantly altered the conformation of septin-9 protein, thereby impairing the microtubule binding and bundling ability. Although the affected members shared a common recurrent mutation, they have a wide spectrum of clinical variability. This may be due to the variable penetrance of the mutation and different epigenetic influences in the family. This is the first genetically confirmed case series of HNA reported from India.
Identifiants
pubmed: 39428775
doi: 10.4103/neurol-india.NI_823_19
pii: 02223311-202409000-00016
doi:
Substances chimiques
Septins
EC 3.6.1.-
SEPTIN9 protein, human
EC 3.6.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1021-1026Informations de copyright
Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.
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