Genetic and clinical characteristics of NEFL -related Charcot-Marie-Tooth disease

Journal of Neurology, Neurosurgery, and Psychiatry
Alejandro HorgaMary M Reilly

Abstract

To analyse and describe the clinical and genetic spectrum of Charcot-Marie-Tooth disease (CMT) caused by mutations in the neurofilament light polypeptide gene (NEFL). Combined analysis of newly identified patients with NEFL-related CMT and all previously reported cases from the literature. Five new unrelated patients with CMT carrying the NEFL mutations P8R and N98S and the novel variant L311P were identified. Combined data from these cases and 62 kindreds from the literature revealed four common mutations (P8R, P22S, N98S and E396K) and three mutational hotspots accounting for 37 (55%) and 50 (75%) kindreds, respectively. Eight patients had de novo mutations. Loss of large-myelinated fibres was a uniform feature in a total of 21 sural nerve biopsies and 'onion bulb' formations and/or thin myelin sheaths were observed in 14 (67%) of them. The neurophysiological phenotype was broad but most patients with E90K and N98S had upper limb motor conduction velocities <38 m/s. Age of onset was ≤3 years in 25 cases. Pyramidal tract signs were described in 13 patients and 7 patients were initially diagnosed with or tested for inherited ataxia. Patients with E90K and N98S frequently presented before age 3 years and developed hearing loss o...Continue Reading

References

Oct 24, 2002·Human Molecular Genetics·Janet BrownleesChristopher C J Miller
Dec 17, 2002·Neurogenetics·Donna-Maria GeorgiouKyproula Christodoulou
Jul 3, 2004·The British Journal of Psychiatry : the Journal of Mental Science·Frans de JongheJack Dekker
Apr 29, 2005·Journal of Neurochemistry·Raül Pérez-OlléRonald K H Liem
Feb 3, 2006·Human Molecular Genetics·Takahiro SasakiShin-Ichi Hisanaga
Apr 19, 2006·American Journal of Medical Genetics. Part a·Conrad L LeungRonald K H Liem
Jun 16, 2006·Neuromolecular Medicine·Garth Nicholson, Simon Myers
Oct 21, 2006·Brain : a Journal of Neurology·Gian Maria FabriziNicoló Rizzuto
Jul 11, 2007·Archives of Neurology·Gabriel Miltenberger-MiltenyiWolfgang N Löscher
Nov 21, 2007·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·Dusan ButinarKyproula Christodoulou
Sep 2, 2008·Journal of Human Genetics·Ji Soo ShinByung-Ok Choi
Jan 17, 2009·European Journal of Cell Biology·Darran M YatesChristopher C J Miller
Mar 17, 2009·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Satyakam BhagavatiWeimin Xu
Dec 30, 2009·Annals of Neurology·Sabrina W YumSteven S Scherer
Aug 16, 2011·Brain : a Journal of Neurology·Jonathan BaetsPeter De Jonghe
Oct 19, 2011·Journal of the Peripheral Nervous System : JPNS·Sinéad M MurphyDavide Pareyson
Dec 14, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Benoit J GentilHeather D Durham
Sep 8, 2012·Journal of Cell Science·Aidong YuanRalph A Nixon
Aug 6, 2014·Journal of Neurology, Neurosurgery, and Psychiatry·Yu-Ichi NotoToshiki Mizuno
Nov 29, 2014·Journal of the Peripheral Nervous System : JPNS·Fiore ManganelliLucio Santoro
Nov 29, 2014·Journal of Neurology, Neurosurgery, and Psychiatry·V FridmanUNKNOWN Inherited Neuropathies Consortium
Jan 15, 2015·Journal of the Peripheral Nervous System : JPNS·Akihiro HashiguchiHiroshi Takashima
Jan 24, 2015·Molecular Genetics & Genomic Medicine·Christina DiVincenzoJoseph J Higgins
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Mar 25, 2015·Molecular Genetics & Genomic Medicine·Alexander P DrewMarina L Kennerson

❮ Previous
Next ❯

Citations

Aug 9, 2019·Molecular Genetics & Genomic Medicine·Justine LeratAnne-Sophie Lia
Nov 13, 2019·Clinical Pharmacology and Therapeutics·Renata MacielMario A Saporta
Feb 9, 2020·Cells·Diana C Muñoz-LassoPilar Gonzalez-Cabo
May 15, 2020·Brain : a Journal of Neurology·Arie R GafsonPaul M Matthews
Jun 12, 2018·Neurology. Genetics·Markus T SainioHenna Tyynismaa
Nov 9, 2019·Journal of the Peripheral Nervous System : JPNS·Diana C LeeSteven S Scherer
Dec 29, 2020·Neuroscience Letters·Kathryn R MossAhmet Höke
Sep 27, 2020·Parkinsonism & Related Disorders·Karlien MulBart P C van de Warrenburg
Feb 19, 2021·Frontiers in Cell and Developmental Biology·Cara R SchiavonUri Manor

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.

Ataxia

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxias (MDS)

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Cardiac Conduction System

The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Discover the latest research on the cardiac conduction system here.

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.