Identification of KMT2D and KDM6A mutations by exome sequencing in Korean patients with Kabuki syndrome
Identification of KMT2D and KDM6A mutations by exome sequencing in Korean patients with Kabuki syndrome
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DOI：
10.1038/jhg.2014.25
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发表时间：
2014-06-01
影响因子：
3.5
通讯作者：
Jeong, Seon-Yong
中科院分区：
文献类型：
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作者：
Cheon, Chong Kun;Sohn, Young Bae;Jeong, Seon-Yong
歌舞伎综合征（KS）（OMIM#147920）是一种多发性先天性异常/精神发育迟滞综合征。最近，KMT 2D和KDM 6A中的致病性变体被确定为55.8-80.0%患者的KS的原因。为了进一步阐明韩国KS患者的分子特征，我们筛选了一组临床确诊KS患者的KMT 2D和KDM 6A突变。在12例临床怀疑KS的患者中进行全外显子组测序和直接测序验证。在11例（91.7%）患者中发现了KMT 2D和KDM 6A突变。未观察到复发突变，发现的11个突变中有10个是新突变。在10例患者中检测到KMT 2D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。一个女孩在KDM 6A中有一个新的剪接位点突变。每个病人都有一个独特的个体突变。这是韩国KS患者通过外显子组测序进行突变分析的第一份报告。由于本研究的突变检出率较高，因此KMT 2D和KDM 6A的严格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。
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.