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Update of the genotype and phenotype of KMT2D and KDM6A by genetic screening of 100 patients with clinically suspected Kabuki syndrome
Author(s) -
Murakami Hiroaki,
Tsurusaki Yoshinori,
Enomoto Keisuke,
Kuroda Yukiko,
Yokoi Takayuki,
Furuya Noritaka,
Yoshihashi Hiroshi,
Minatogawa Mari,
AbeHatano Chihiro,
Ohashi Ikuko,
Nishimura Naoto,
Kumaki Tatsuro,
Enomoto Yumi,
Naruto Takuya,
Iwasaki Fuminori,
Harada Noriaki,
Ishikawa Aki,
Kawame Hiroshi,
Sameshima Kiyoko,
Yamaguchi Yu,
Kobayashi Masahisa,
Tominaga Makiko,
Ishikiriyama Satoshi,
Tanaka Toshiaki,
Suzumura Hiroshi,
Ninomiya Shinsuke,
Kondo Akane,
Kaname Tadashi,
Kosaki Kenjiro,
Masuno Mitsuo,
Kuroki Yoshikazu,
Kurosawa Kenji
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61793
Subject(s) - kabuki syndrome , phenotype , genetics , kabuki , medicine , intellectual disability , rna splicing , gene , biology , rna , art , visual arts
Abstract Kabuki syndrome is characterized by a variable degree of intellectual disability, characteristic facial features, and complications in various organs. Many variants have been identified in two causative genes, that is, lysine methyltransferase 2D ( KMT2D ) and lysine demethylase 6A ( KDM6A ). In this study, we present the results of genetic screening of 100 patients with a suspected diagnosis of Kabuki syndrome in our center from July 2010 to June 2018. We identified 76 variants (43 novel) in KMT2D and 4 variants (3 novel) in KDM6A as pathogenic or likely pathogenic. Rare variants included a deep splicing variant (c.14000‐8C>G) confirmed by RNA sequencing and an 18% mosaicism level for a KMT2D mutation. We also characterized a case with a blended phenotype consisting of Kabuki syndrome, osteogenesis imperfecta, and 16p13.11 microdeletion. We summarized the clinical phenotypes of 44 patients including a patient who developed cervical cancer of unknown origin at 16 years of age. This study presents important details of patients with Kabuki syndrome including rare clinical cases and expands our genetic understanding of this syndrome, which will help clinicians and researchers better manage and understand patients with Kabuki syndrome they may encounter.