KMT2B rare missense variants in generalized dystonia.
Mov Disord
; 32(7): 1087-1091, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-28520167
ABSTRACT
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. © 2017 International Parkinson and Movement Disorder Society.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Histona-Lisina N-Metiltransferase
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Distúrbios Distônicos
Tipo de estudo:
Guideline
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Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article