Recessive null-allele variants in MAG associated with spastic ataxia, nystagmus, neuropathy, and dystonia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F20%3A10416033" target="_blank" >RIV/00216208:11110/20:10416033 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/20:10416033

Výsledek na webu

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

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.parkreldis.2020.06.027" target="_blank" >10.1016/j.parkreldis.2020.06.027</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Recessive null-allele variants in MAG associated with spastic ataxia, nystagmus, neuropathy, and dystonia

Popis výsledku v původním jazyce

Introduction: The gene encoding myelin-associated glycoprotein (MAG) has been implicated in autosomal-recessive spastic paraplegia type 75. To date, only four families with biallelic missense variants in MAG have been reported. The genotypic and phenotypic spectrum of MAG-associated disease awaits further elucidation. Methods: Four unrelated patients with complex neurologic conditions underwent whole-exome sequencing within research or diagnostic settings. Following determination of the underlying genetic defects, in-depth phenotyping and literature review were performed. Results: In all case subjects, we detected ultra-rare homozygous or compound heterozygous variants in MAG. The observed nonsense (c.693C &gt; A [p.Tyr231*], c.980G &gt; A [p.Trp327*], c.1126C &gt; T [p.Gln376*], and 1522C &gt; T [p.Arg508*]) and frameshift (c.517_521dupAGCTG [p.Trp174*]) alleles were predicted to result in premature termination of protein translation. Affected patients presented with variable combinations of psychomotor delay, ataxia, eye movement abnormalities, spasticity, dystonia, and neuropathic symptoms. Cerebellar signs, nystagmus, and pyramidal tract dysfunction emerged as unifying features in the majority of MAG-mutated individuals identified to date. Conclusions: Our study is the first to describe biallelic null variants in MAG, confirming that loss of myelin-associated glycoprotein causes severe infancy-onset disease with central and peripheral nervous system involvement.

Název v anglickém jazyce

Recessive null-allele variants in MAG associated with spastic ataxia, nystagmus, neuropathy, and dystonia

Popis výsledku anglicky

Introduction: The gene encoding myelin-associated glycoprotein (MAG) has been implicated in autosomal-recessive spastic paraplegia type 75. To date, only four families with biallelic missense variants in MAG have been reported. The genotypic and phenotypic spectrum of MAG-associated disease awaits further elucidation. Methods: Four unrelated patients with complex neurologic conditions underwent whole-exome sequencing within research or diagnostic settings. Following determination of the underlying genetic defects, in-depth phenotyping and literature review were performed. Results: In all case subjects, we detected ultra-rare homozygous or compound heterozygous variants in MAG. The observed nonsense (c.693C &gt; A [p.Tyr231*], c.980G &gt; A [p.Trp327*], c.1126C &gt; T [p.Gln376*], and 1522C &gt; T [p.Arg508*]) and frameshift (c.517_521dupAGCTG [p.Trp174*]) alleles were predicted to result in premature termination of protein translation. Affected patients presented with variable combinations of psychomotor delay, ataxia, eye movement abnormalities, spasticity, dystonia, and neuropathic symptoms. Cerebellar signs, nystagmus, and pyramidal tract dysfunction emerged as unifying features in the majority of MAG-mutated individuals identified to date. Conclusions: Our study is the first to describe biallelic null variants in MAG, confirming that loss of myelin-associated glycoprotein causes severe infancy-onset disease with central and peripheral nervous system involvement.

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/NV19-04-00233" target="_blank" >NV19-04-00233: Klinické, zobrazovací a biologické prediktory účinků hluboké mozkové stimulace u Parkinsonovy nemoci</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

Parkinsonism and Related Disorders

ISSN

1353-8020

e-ISSN

—

Svazek periodika

77

Číslo periodika v rámci svazku

August

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

70-75

Kód UT WoS článku

000578015000016

EID výsledku v databázi Scopus

2-s2.0-85087294875