Demyelinating Charcot Marie Tooth neuropathy associated with FBLN5 mutations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F20%3A10413222" target="_blank" >RIV/00216208:11130/20:10413222 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064203:_____/20:10413222

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=v4k01nSFDS" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=v4k01nSFDS</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/ene.14463" target="_blank" >10.1111/ene.14463</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Demyelinating Charcot Marie Tooth neuropathy associated with FBLN5 mutations

Popis výsledku v původním jazyce

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease type 1 (CMT1) is a group of autosomal-dominantly inherited demyelinating sensorimotor neuropathies. Symptoms usually start in the 1(st) -2(nd) decade and include distal muscle weakness and wasting, sensory disturbances and foot deformities. The most frequent cause is a duplication of PMP22 while point mutations in PMP22 and other genes are rare causes. Recently, FBLN5 mutations have been reported in CMT1 families. METHODS: Individuals with FBLN5-associated CMT1 were compiled from clinical and research genetic testing laboratories. Clinical data were extracted from medical records or obtained during patients&apos; visits at our centres or primary care sites. RESULTS: We ascertained 19 CMT1 families containing 38 carriers of three different FBLN5 missense variants and confirmed a mutational hot spot at c.1117C&gt;T (p.Arg373Cys). Compared to patients with the common PMP22 duplication, individuals with FBLN5 variants had later age of diagnosis (3(rd) -5(th) decade) and less severely reduced motor median nerve conduction velocities (around 31 m/s). The most frequent clinical presentations were prominent sensory disturbances and painful sensations, often as initial symptom and pronounced in the upper limbs, contrasting with rather mild to moderate motor deficits. CONCLUSIONS: Our study confirms the relevance of FBLN5 mutations in CMT1. We propose to include FBLN5 in the genetic work-up of individuals suspected with CMT1, particularly when diagnosis is established beyond the 1(st) -2(nd) decade and comparably moderate motor deficits contrast with early and marked sensory involvement. FBLN5-associated CMT1 has a recognizable clinical phenotype and should be referred to as CMT1H according to the current classification scheme.

Název v anglickém jazyce

Demyelinating Charcot Marie Tooth neuropathy associated with FBLN5 mutations

Popis výsledku anglicky

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease type 1 (CMT1) is a group of autosomal-dominantly inherited demyelinating sensorimotor neuropathies. Symptoms usually start in the 1(st) -2(nd) decade and include distal muscle weakness and wasting, sensory disturbances and foot deformities. The most frequent cause is a duplication of PMP22 while point mutations in PMP22 and other genes are rare causes. Recently, FBLN5 mutations have been reported in CMT1 families. METHODS: Individuals with FBLN5-associated CMT1 were compiled from clinical and research genetic testing laboratories. Clinical data were extracted from medical records or obtained during patients&apos; visits at our centres or primary care sites. RESULTS: We ascertained 19 CMT1 families containing 38 carriers of three different FBLN5 missense variants and confirmed a mutational hot spot at c.1117C&gt;T (p.Arg373Cys). Compared to patients with the common PMP22 duplication, individuals with FBLN5 variants had later age of diagnosis (3(rd) -5(th) decade) and less severely reduced motor median nerve conduction velocities (around 31 m/s). The most frequent clinical presentations were prominent sensory disturbances and painful sensations, often as initial symptom and pronounced in the upper limbs, contrasting with rather mild to moderate motor deficits. CONCLUSIONS: Our study confirms the relevance of FBLN5 mutations in CMT1. We propose to include FBLN5 in the genetic work-up of individuals suspected with CMT1, particularly when diagnosis is established beyond the 1(st) -2(nd) decade and comparably moderate motor deficits contrast with early and marked sensory involvement. FBLN5-associated CMT1 has a recognizable clinical phenotype and should be referred to as CMT1H according to the current classification scheme.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/NV16-31921A" target="_blank" >NV16-31921A: Neznámá příčina DFNB1 hluchoty u pacientů s pouze jednou patogenní mutací v GJB2 genu – komplexní analýza pomocí nových molekulárně genetických metod.</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Neurology

ISSN

1351-5101

e-ISSN

—

Svazek periodika

27

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

2568-2574

Kód UT WoS článku

000565913100001

EID výsledku v databázi Scopus

2-s2.0-85090140177