KMT2B rare missense variants in generalized dystonia

Movement Disorders : Official Journal of the Movement Disorder Society
Michael ZechJuliane Winkelmann

Abstract

Recently a novel syndrome of childhood-onset generalized dystonia originating from mutations in lysine-specific methyltransferase 2B (KMT2B) has been reported. 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. 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. Rare missense variation in KMT2B represents an additional cause of generalized dystonia. Application of sequence interpretation standards is required before assigning pathogenicity to a K...Continue Reading

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Citations

Nov 1, 2017·Current Neurology and Neuroscience Reports·Miryam Carecchio, Niccolò E Mencacci
Jun 20, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Miryam CarecchioNardo Nardocci
Apr 4, 2020·Journal of Movement Disorders·Jun Kyu MunJinyoung Youn
Sep 5, 2020·Annals of Clinical and Translational Neurology·Shiro HorisawaTakaomi Taira
Jun 6, 2019·Journal of Human Genetics·Hormos Salimi DafsariSebahattin Cirak
Nov 27, 2019·Current Neurology and Neuroscience Reports·Michael ZechJuliane Winkelmann
Sep 22, 2018·Nature Reviews. Disease Primers·Bettina BalintKailash P Bhatia
Jan 24, 2020·Movement Disorders Clinical Practice·Ziqiang CaoHaibo Yang
Jan 28, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Lara M LangeKatja Lohmann
Mar 20, 2021·Journal of Neural Transmission·Han-Joon Kim, Beomseok Jeon
Apr 15, 2018·Parkinsonism & Related Disorders·Toshitaka KawaraiRyuji Kaji

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