KMT2B Rare Missense Variants in Generalized Dystonia

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F17%3A10361107" target="_blank" >RIV/00064165:_____/17:10361107 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/17:10361107 RIV/00023884:_____/12:00007435
Result on the web
<a href="http://dx.doi.org/10.1002/mds.27026" target="_blank" >http://dx.doi.org/10.1002/mds.27026</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/mds.27026" target="_blank" >10.1002/mds.27026</a>

Result language
angličtina
Original language name
KMT2B Rare Missense Variants in Generalized Dystonia
Original language description
Background: Recently a novel syndrome of childhood-onset generalized dystonia originating from mutations in lysine-specific methyltransferase 2B (KMT2B) has been reported. Methods: We sequenced the exomes of 4 generalized dystonia-affected probands recruited from a Prague movement disorders center (Czech Republic). Bioinformatics analyses were conducted to select candidate causal variants in described dystonia-mutated genes. After cosegregation testing, checklists from the American College of Medical Genetics and Genomics were adopted to judge variant pathogenicity. Results: Three novel, predicted protein-damaging missense variants in KMT2B were identified (p.Glu1234Lys, p.Ala1541Val, p.Arg1779Gln). Meeting pathogenicity criteria, p.Glu1234Lys was absent from population-based controls, situated in a key protein domain, and had occurred de novo. The associated phenotype comprised adolescence-onset generalized isolated dystonia with prominent speech impairment. Although linked to a similar clinical expression, p.Ala1541Val and p.Arg1779Gln remained of uncertain significance. Conclusions: Rare missense variation in KMT2B represents an additional cause of generalized dystonia. Application of sequence interpretation standards is required before assigning pathogenicity to a KMT2B missense variant.
Czech name
—
Czech description
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Type
J<sub>imp</sub> - 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/GA16-13323S" target="_blank" >GA16-13323S: MIcro and MAcro Connectomics of the Subthalamic nucleus in humans: impact of neuromodulation and dopamine depletion</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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