Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
Genet Med. 2021 Jul;23(7):1202-1210. doi: 10.1038/s41436-021-01119-8. Epub 2021 Mar 5.
The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood.
Genetic and clinical details of new and published individuals with pathogenic KDM6A variants were compiled and analyzed.
Sixty-one distinct pathogenic KDM6A variants (50 truncating, 11 missense) from 80 patients (34 males, 46 females) were identified. Missense variants clustered in the TRP 2, 3, 7 and Jmj-C domains. Truncating variants were significantly more likely to be de novo. Thirteen individuals had maternally inherited variants and one had a paternally inherited variant. Neonatal feeding difficulties, hypoglycemia, postnatal growth retardation, poor weight gain, motor delay, intellectual disability (ID), microcephaly, congenital heart anomalies, palate defects, renal malformations, strabismus, hearing loss, recurrent infections, hyperinsulinism, seizures, joint hypermobility, and gastroesophageal reflux were frequent clinical findings. Facial features of over a third of patients were not typical for KS. Males were significantly more likely to be born prematurely, have shorter stature, and severe developmental delay/ID.
We expand the KDM6A variant spectrum and delineate the KS2 phenotype. We demonstrate that the variability of the KS2 phenotypic depends on sex and the variant type. We also highlight the overlaps and differences between the phenotypes of KS2 and KS1.
X 连锁歌舞伎综合征 2 型（KS2）的变异谱和表型了解甚少。
对新发现的和已发表的具有致病性 KDM6A 变异的个体的遗传和临床详细信息进行了编译和分析。
从 80 名患者（34 名男性，46 名女性）中鉴定出 61 种不同的致病性 KDM6A 变异（50 种截断，11 种错义）。错义变异集中在 TRP2、3、7 和 Jmj-C 结构域。截断变异明显更可能是新生的。13 名患者携带母系遗传变异，1 名患者携带父系遗传变异。新生儿喂养困难、低血糖、出生后生长迟缓、体重增长不良、运动发育迟缓、智力残疾（ID）、小头畸形、先天性心脏畸形、腭裂、肾脏畸形、斜视、听力损失、反复感染、高胰岛素血症、癫痫发作、关节过度活动和胃食管反流是常见的临床发现。超过三分之一患者的面部特征不符合 KS 的典型特征。男性更有可能早产、身材矮小和严重发育迟缓/智力残疾。
我们扩展了 KDM6A 变异谱并描绘了 KS2 表型。我们证明，KS2 表型的可变性取决于性别和变异类型。我们还强调了 KS2 和 KS1 表型之间的重叠和差异。
