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

Result code in 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>

Alternative codes found

RIV/00064165:_____/20:10416033

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

<a href="/en/project/NV19-04-00233" target="_blank" >NV19-04-00233: Clinical, Imaging and Biological predictors of effects associated with deep brain stimulation in Parkinson’s disease</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

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

Name of the periodical

Parkinsonism and Related Disorders

ISSN

1353-8020

e-ISSN

—

Volume of the periodical

77

Issue of the periodical within the volume

August

Country of publishing house

GB - UNITED KINGDOM

Number of pages

6

Pages from-to

70-75

UT code for WoS article

000578015000016

EID of the result in the Scopus database

2-s2.0-85087294875