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Zech, M. ; Jech, R.* ; Havránková, P.* ; Fečíková, A.* ; Berutti, R. ; Urgošík, D.* ; Kemlink, D.* ; Strom, T.M. ; Roth, J.* ; Růžička, E.* ; Winkelmann, J.

KMT2B rare missense variants in generalized dystonia.

Mov. Disord. 32, 1087-1091 (2017)
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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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Kmt2b ; Dystonia ; Exome ; Rare Missense Variants; Classification; Phenomenology; Mutations; Update
ISSN (print) / ISBN 0885-3185
e-ISSN 1531-8257
Zeitschrift Movement Disorders
Quellenangaben Band: 32, Heft: 7, Seiten: 1087-1091 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken