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An inherited KMT2B duplication variant in a Chinese family with dystonia and/or development delay

2018; Elsevier BV; Volume: 63; Linguagem: Inglês

10.1016/j.parkreldis.2018.08.021

1873-5126

Lifang Dai, Changhong Ding, Fang Fang,

Genomics and Rare Diseases

Dystonia is a hyperkinetic movement disorder characterized by sustained or intermittent muscle contractions causing repetitive twisting movements and disabling postures [ [1] Lumsden D.E. Gimeno H. Lin J.P. Classification of dystonia in childhood. Park. Relat. Disord. 2016; 33: 138-141 Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar ]. Since 2016, KMT2B, a gene encoding lysine methyltransferase 2B, has been reported to be an important cause of childhood-onset progressive generalized dystonia with or without pre-existing development delay [ 2 Zech M. Boesch S. Maier E.M. et al. Haploinsufficiency of KMT2B, encoding the lysine specific histone methyltransferase 2B, results in early-onset generalized dystonia. Am. J. Hum. Genet. 2016; 99: 1377-1387 Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar , 3 Baizabal-Carvallo J.F. Alonso-Juarez M. Generalized dystonia associated with mutation in the histone methyltransferase gene KMT2B (DYT28) and white matter abnormalities. Park. Relat. Disord. 2018; 49: 116-117 Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar , 4 Faundes V. Newman W.G. Bernardini L. et al. Histone lysine methylases and demethylases in the landscap of human developmental disorders. Am. J. Hum. Genet. 2018; 102: 175-187 Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar ]. The presence of both symptomatic and asymptomatic carriers and relatives suggests incomplete penetrance, and symptomatic parents appear to have later onset dystonia with fewer systemic features than their children [ [5] Gorman K.M. Meyer E. Kurian M.A. Review of the phenotype of early-onset generalised progressive dystonia due to mutations in KMT2B. Eur. J. Paediatr. Neurol. 2018; 22: 245-256 Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar , [6] Meyer E. Carss K.J. Rankin J. et al. Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia. Nat. Genet. 2017; 49: 223-237 Crossref PubMed Scopus (139) Google Scholar ]. Most KMT2B variants reported are de novo. To our knowledge, there are no previous reports of multiple patients with the same KMT2B variant with dystonia and development delay in one family. However, there is evidence of other relatives within the family having isolated development delay without dystonia. We describe a Chinese family with an inherited KMT2B duplication variant.