Cheon Chong Kun, Sohn Young Bae, Ko Jung Min, Lee Yeoun Joo, Song Ji Sun, Moon Jea Woo, Yang Bo Kyoung, Ha Il Soo, Bae Eun Jung, Jin Hyun-Seok, Jeong Seon-Yong
1] Department of Pediatrics, Pediatric Genetics and Metabolism, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, South Korea [2] Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea.
Department of Medical Genetics, Ajou University School of Medicine, Suwon, South Korea.
J Hum Genet. 2014 Jun;59(6):321-5. doi: 10.1038/jhg.2014.25. Epub 2014 Apr 17.
Kabuki syndrome (KS) (OMIM#147920) is a multiple congenital anomaly/mental retardation syndrome. Recently, pathogenic variants in KMT2D and KDM6A were identified as the causes of KS in 55.8-80.0% of patients. To elucidate further the molecular characteristics of Korean patients with KS, we screened a cohort of patients with clinically defined KS for mutations in KMT2D and KDM6A. Whole-exome sequencing and direct sequencing for validation were performed in 12 patients with a clinical suspicion of KS. KMT2D and KDM6A mutations were identified in 11 (91.7%) patients. No recurrent mutation was observed, and 10 out of the 11 mutations found were novel. KMT2D mutations were detected in 10 patients, including four small deletions or insertions and four nonsense and two missense mutations. One girl had a novel splice-site mutation in KDM6A. Each patient had a unique individual mutation. This is the first report of mutational analysis via exome sequencing in Korean patients with KS. Because the mutation-detection rate was high in this study, rigorous mutation analysis of KMT2D and KDM6A may be an important tool for the early diagnosis and genetic counseling of Korean patients with KS.
歌舞伎综合征（KS）（OMIM#147920）是一种多发性先天性异常/智力障碍综合征。最近，KMT2D和KDM6A的致病变异被确定为55.8%-80.0%的KS患者的病因。为了进一步阐明韩国KS患者的分子特征，我们对一组临床诊断为KS的患者进行了KMT2D和KDM6A突变筛查。对12例临床疑似KS的患者进行了全外显子组测序及用于验证的直接测序。在11例（91.7%）患者中发现了KMT2D和KDM6A突变。未观察到复发性突变，所发现的11个突变中有10个是新的。在10例患者中检测到KMT2D突变，包括4个小缺失或插入、4个无义突变和2个错义突变。1名女孩在KDM6A中有一个新的剪接位点突变。每个患者都有独特的个体突变。这是韩国KS患者通过外显子组测序进行突变分析的首份报告。由于本研究中的突变检测率很高，对KMT2D和KDM6A进行严格的突变分析可能是韩国KS患者早期诊断和遗传咨询的重要工具。
