Spectrum of Clinical Variability with SEPT9 Gene Mutation in Hereditary Neuralgic Amyotrophy: Understanding the Pathogenesis Using Molecular Dynamics Simulation Study.

Autor:	Bhatti A; Department of Neurology, Seth GS Medical College and KEM Hospital, Acharya Donde Marg, Maharashtra, India., Ravat S; Department of Neurology, Seth GS Medical College and KEM Hospital, Acharya Donde Marg, Maharashtra, India., Desai K; Department of Neurology, Seth GS Medical College and KEM Hospital, Acharya Donde Marg, Maharashtra, India., Shekhar BR; Department of Genetics, ICMR-National Institute for Research in Reproductive Health (ICMR-NIRRH), Jahangir Merwanji Street, Maharashtra, India., Menon SR; Department of Genetics, ICMR-National Institute for Research in Reproductive Health (ICMR-NIRRH), Jahangir Merwanji Street, Maharashtra, India., Kumbhar BV; Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India., Kunwar A; Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India., Jain N; Department of Neurology, Seth GS Medical College and KEM Hospital, Acharya Donde Marg, Maharashtra, India., Das DK; Department of Genetics, ICMR-National Institute for Research in Reproductive Health (ICMR-NIRRH), Jahangir Merwanji Street, Maharashtra, India.
Jazyk:	angličtina
Zdroj:	Neurology India [Neurol India] 2024 Sep 01; Vol. 72 (5), pp. 1021-1026. Date of Electronic Publication: 2024 Oct 19.
DOI:	10.4103/neurol-india.NI_823_19
Abstrakt:	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: In this study, we have investigated the phenotypic and genetic features in a large pedigree with HNA. 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: 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. (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)
Databáze:	MEDLINE
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