Neurofascin (NFASC) gene mutation causes autosomal recessive ataxia with demyelinating neuropathy

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Introduction: Neurofascin, encoded by NFASC, is a transmembrane protein that plays an essential role in nervous system development and node of Ranvier function. Anti-Neurofascin autoantibodies cause a specific type of chronic inflammatory demyelinating polyneuropathy (CIDP) often characterized by cerebellar ataxia and tremor. Recently, homozygous NFASC mutations were recently associated with a neurodevelopmental disorder in two families. Methods: A combined approach of linkage analysis and whole-exome sequencing was performed to find the genetic cause of early-onset cerebellar ataxia and demyelinating neuropathy in two siblings from a consanguineous Italian family. Functional studies were conducted on neurons from induced pluripotent stem cells (iPSCs) generated from the patients. Results: Genetic analysis revealed a homozygous p.V1122E mutation in NFASC. This mutation, affecting a highly conserved hydrophobic transmembrane domain residue, led to significant loss of Neurofascin protein in the iPSC-derived neurons of affected siblings. Conclusions: The identification of NFASC mutations paves the way for genetic research in the developing field of nodopathies, an emerging pathological entity involving the nodes of Ranvier, which are associated for the first time with a hereditary ataxia syndrome with neuropathy.

Original languageEnglish
Pages (from-to)66-72
JournalParkinsonism and Related Disorders
Volume63
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Ataxia
Ranvier's Nodes
Spinocerebellar Degenerations
Induced Pluripotent Stem Cells
Mutation
Genes
Siblings
Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Exome
Neurons
Cerebellar Ataxia
Genetic Research
Tremor
Autoantibodies
Nervous System
Proteins

Keywords

  • Hereditary Ataxia
  • Neurofascin
  • Neuropathy
  • NFASC
  • Nodopathy

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

@article{893d2a60407a4dd19d61a58134cc0da1,
title = "Neurofascin (NFASC) gene mutation causes autosomal recessive ataxia with demyelinating neuropathy",
abstract = "Introduction: Neurofascin, encoded by NFASC, is a transmembrane protein that plays an essential role in nervous system development and node of Ranvier function. Anti-Neurofascin autoantibodies cause a specific type of chronic inflammatory demyelinating polyneuropathy (CIDP) often characterized by cerebellar ataxia and tremor. Recently, homozygous NFASC mutations were recently associated with a neurodevelopmental disorder in two families. Methods: A combined approach of linkage analysis and whole-exome sequencing was performed to find the genetic cause of early-onset cerebellar ataxia and demyelinating neuropathy in two siblings from a consanguineous Italian family. Functional studies were conducted on neurons from induced pluripotent stem cells (iPSCs) generated from the patients. Results: Genetic analysis revealed a homozygous p.V1122E mutation in NFASC. This mutation, affecting a highly conserved hydrophobic transmembrane domain residue, led to significant loss of Neurofascin protein in the iPSC-derived neurons of affected siblings. Conclusions: The identification of NFASC mutations paves the way for genetic research in the developing field of nodopathies, an emerging pathological entity involving the nodes of Ranvier, which are associated for the first time with a hereditary ataxia syndrome with neuropathy.",
keywords = "Hereditary Ataxia, Neurofascin, Neuropathy, NFASC, Nodopathy",
author = "Edoardo Monfrini and Letizia Straniero and Sara Bonato and {Monzio Compagnoni}, Giacomo and Andreina Bordoni and Robertino Dilena and Paola Rinchetti and Rosamaria Silipigni and Dario Ronchi and Stefania Corti and Comi, {Giacomo P.} and Nereo Bresolin and Stefano Duga and {Di Fonzo}, Alessio",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.parkreldis.2019.02.045",
language = "English",
volume = "63",
pages = "66--72",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Neurofascin (NFASC) gene mutation causes autosomal recessive ataxia with demyelinating neuropathy

AU - Monfrini, Edoardo

AU - Straniero, Letizia

AU - Bonato, Sara

AU - Monzio Compagnoni, Giacomo

AU - Bordoni, Andreina

AU - Dilena, Robertino

AU - Rinchetti, Paola

AU - Silipigni, Rosamaria

AU - Ronchi, Dario

AU - Corti, Stefania

AU - Comi, Giacomo P.

AU - Bresolin, Nereo

AU - Duga, Stefano

AU - Di Fonzo, Alessio

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Introduction: Neurofascin, encoded by NFASC, is a transmembrane protein that plays an essential role in nervous system development and node of Ranvier function. Anti-Neurofascin autoantibodies cause a specific type of chronic inflammatory demyelinating polyneuropathy (CIDP) often characterized by cerebellar ataxia and tremor. Recently, homozygous NFASC mutations were recently associated with a neurodevelopmental disorder in two families. Methods: A combined approach of linkage analysis and whole-exome sequencing was performed to find the genetic cause of early-onset cerebellar ataxia and demyelinating neuropathy in two siblings from a consanguineous Italian family. Functional studies were conducted on neurons from induced pluripotent stem cells (iPSCs) generated from the patients. Results: Genetic analysis revealed a homozygous p.V1122E mutation in NFASC. This mutation, affecting a highly conserved hydrophobic transmembrane domain residue, led to significant loss of Neurofascin protein in the iPSC-derived neurons of affected siblings. Conclusions: The identification of NFASC mutations paves the way for genetic research in the developing field of nodopathies, an emerging pathological entity involving the nodes of Ranvier, which are associated for the first time with a hereditary ataxia syndrome with neuropathy.

AB - Introduction: Neurofascin, encoded by NFASC, is a transmembrane protein that plays an essential role in nervous system development and node of Ranvier function. Anti-Neurofascin autoantibodies cause a specific type of chronic inflammatory demyelinating polyneuropathy (CIDP) often characterized by cerebellar ataxia and tremor. Recently, homozygous NFASC mutations were recently associated with a neurodevelopmental disorder in two families. Methods: A combined approach of linkage analysis and whole-exome sequencing was performed to find the genetic cause of early-onset cerebellar ataxia and demyelinating neuropathy in two siblings from a consanguineous Italian family. Functional studies were conducted on neurons from induced pluripotent stem cells (iPSCs) generated from the patients. Results: Genetic analysis revealed a homozygous p.V1122E mutation in NFASC. This mutation, affecting a highly conserved hydrophobic transmembrane domain residue, led to significant loss of Neurofascin protein in the iPSC-derived neurons of affected siblings. Conclusions: The identification of NFASC mutations paves the way for genetic research in the developing field of nodopathies, an emerging pathological entity involving the nodes of Ranvier, which are associated for the first time with a hereditary ataxia syndrome with neuropathy.

KW - Hereditary Ataxia

KW - Neurofascin

KW - Neuropathy

KW - NFASC

KW - Nodopathy

UR - http://www.scopus.com/inward/record.url?scp=85062362249&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062362249&partnerID=8YFLogxK

U2 - 10.1016/j.parkreldis.2019.02.045

DO - 10.1016/j.parkreldis.2019.02.045

M3 - Article

AN - SCOPUS:85062362249

VL - 63

SP - 66

EP - 72

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

SN - 1353-8020

ER -