Department of Pediatric Genetics, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Turkey.
Department of Medical Genetics, Bezmialem University, Medical School, Istanbul, Turkey.
Am J Med Genet A. 2022 Oct;188(10):2976-2987. doi: 10.1002/ajmg.a.62944. Epub 2022 Aug 8.
Kabuki syndrome (KS) is a rare disorder characterized by distinct face, persistent fingertip pads, and intellectual disability (ID) caused by mutation in KMT2D (56%-76%) or KDM6A (5%-8%). Thirty-seven children aged 1-16 years who followed for median of 6.8 years were included in this study, which aimed to investigate the genetic and clinical characteristics of KS patients. KMT2D and KDM6A were evaluated by sequencing and multiplex-ligation-dependent probe amplification in 32 patients. Twenty-one pathogenic variants in KMT2D, of which 17 were truncated and nine were novel, one frame-shift novel variant in KDM6A were identified. The molecular diagnosis rate was 68.7% (22/32). In the whole-exome sequencing analysis performed in the remaining patients, no pathogenic variant that could cause any disease was detected. All patients had ID; 43.2% were severe and moderate. We observed that facial features that became more prominent with age were enough for a possible diagnosis of KS in infancy. The frequencies of facial features, cardiac and renal anomalies, short stature, microcephaly, and epilepsy did not differ depending on whether they had truncating or nontruncating variants or were in variant-negative KS-like group. This study has expanded clinical features of the disease, as well as identified new variants in genes causing KS.
歌舞伎综合征(KS)是一种罕见的疾病,其特征为独特的面容、持续存在的指尖垫和智力障碍(ID),由 KMT2D(56%-76%)或 KDM6A(5%-8%)突变引起。本研究纳入了 37 名年龄在 1-16 岁之间、中位随访时间为 6.8 年的儿童,旨在研究 KS 患者的遗传和临床特征。通过对 32 名患者进行测序和多重连接依赖性探针扩增评估 KMT2D 和 KDM6A。在 KMT2D 中发现了 21 个致病性变异,其中 17 个是截断的,9 个是新的,在 KDM6A 中发现了一个新的移码变异。分子诊断率为 68.7%(22/32)。在对其余患者进行的全外显子组测序分析中,未发现任何可导致任何疾病的致病性变异。所有患者均存在 ID;43.2%为重度和中度。我们观察到,随着年龄的增长,面部特征变得更加明显,足以对婴儿期的 KS 进行可能的诊断。面部特征、心脏和肾脏异常、身材矮小、小头畸形和癫痫的频率与是否存在截断或非截断变异或在变异阴性 KS 样组中无关。本研究扩展了该疾病的临床特征,并鉴定了导致 KS 的基因中的新变异。