Novel KDM6A (UTX) mutations and a clinical and molecular review of the X-linked Kabuki syndrome (KS2)
Novel KDM6A (UTX) mutations and a clinical and molecular review of the X-linked Kabuki syndrome (KS2)
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DOI：
10.1111/cge.12363
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发表时间：
2015-03-01
影响因子：
3.5
通讯作者：
Donnai, D.
中科院分区：
文献类型：
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作者：
Banka, S.;Lederer, D.;Donnai, D.
我们描述了7例KDM6A（位于Xp11.3，编码UTX）突变患者，KDM6A是歌舞伎综合征（KS2, MIM 300867）的罕见病因，并首次报道了该基因的种系错义和剪接位点突变。我们证明，不到5%的歌舞伎综合征是由KDM6A突变引起的。我们的研究表明，与KMT2D（以前称为MLL2）突变引起的常见1型歌舞伎综合征（KS1, MIM 147920）相似，KS2患者的特征是婴儿期张力低下和喂养困难，产后生长不良和身材矮小。与KS1不同，KS2的发育迟缓和学习障碍在男孩中一般为中度至重度，而在女孩中一般为轻度至中度。有些女孩可能发育正常。言语和认知往往比运动发育受到更严重的影响。易受感染，关节松弛，心脏，牙齿和眼科异常是常见的。低血糖在KS2中比在KS1中更常见。面部畸形与KDM6A突变是可变的，诊断面部完形单独可能是困难的一些患者。多毛，长幻觉和大的中门牙可能是一些患者潜在的KDM6A突变的有用线索。
We describe seven patients with KDM6A (located on Xp11.3 and encodes UTX) mutations, a rare cause of Kabuki syndrome (KS2, MIM 300867) and report, for the first time, germ-line missense and splice-site mutations in the gene. We demonstrate that less than 5% cases of Kabuki syndrome are due to KDM6A mutations. Our work shows that similar to the commoner Type 1 Kabuki syndrome (KS1, MIM 147920) caused by KMT2D (previously called MLL2) mutations, KS2 patients are characterized by hypotonia and feeding difficulties during infancy and poor postnatal growth and short stature. Unlike KS1, developmental delay and learning disability are generally moderate-severe in boys but mild-moderate in girls with KS2. Some girls may have a normal developmental profile. Speech and cognition tend to be more severely affected than motor development. Increased susceptibility to infections, join laxity, heart, dental and ophthalmological anomalies are common. Hypoglycaemia is more common in KS2 than in KS1. Facial dysmorphism with KDM6A mutations is variable and diagnosis on facial gestalt alone may be difficult in some patients. Hypertrichosis, long halluces and large central incisors may be useful clues to an underlying KDM6A mutation in some patients.