MLL2 mosaic mutations and intragenic deletion-duplications in patients with Kabuki syndrome
MLL2 mosaic mutations and intragenic deletion-duplications in patients with Kabuki syndrome
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DOI：
10.1111/j.1399-0004.2012.01955.x
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发表时间：
2013-05-01
影响因子：
3.5
通讯作者：
Donnai, D.
中科院分区：
文献类型：
--
作者：
Banka, S.;Howard, E.;Donnai, D.
歌舞伎综合征患者中的班卡·S、霍华德·E、邦斯通·S、钱德勒·柯、可儿·B、拉克伦·K、麦基·S、梅塔·斯格特、塔瓦雷斯·ALT、托尔米·J、唐奈·D·米勒·米勒和基因内缺失-重复突变。临床基因2013：83：467-471。(C)John Wiley&Sons A/S由Blackwell出版有限公司出版，2012年歌舞伎症候群(KS)是一种罕见的多系统障碍，可导致各种先天性畸形、典型畸形和可变学习障碍。在大多数病例中，它是由ML12点突变引起的，很少是由于涉及KDM6A的缺失。近三分之一的案件仍未侦破。在这里，我们通过呈现五名典型的KS患者来扩展已知的遗传学基础，所有患者都有新的MLI2突变类型-两名患者有嵌合体小缺失，一名患者有马赛克全基因缺失，一名患者有多外显子缺失，一名患者有基因内多外显子重复。我们建议对所有患有典型KS的患者进行MLL2剂量研究，在这些患者中，传统的Sanger测序无法识别突变。KS中这种MLL2突变的发生率可能与涉及KDM6A的缺失类似。这些发现可能有助于了解MLL2的突变机制和KS的发病机制。
Banka S, Howard E, Bunstone S, Chandler KE, Kerr B, Lachlan K, McKee S, Mehta SG, Tavares ALT, Tolmie J, Donnai D. MLL2 mosaic mutations and intragenic deletion-duplications in patients with Kabuki syndrome. Clin Genet 2013: 83: 467-471. (C) John Wiley & Sons A/S. Published by Blackwell Publishing Ltd, 2012 Kabuki syndrome (KS) is a rare multi-system disorder that can result in a variety of congenital malformations, typical dysmorphism and variable learning disability. It is caused by MLL2 point mutations in the majority of the cases and, rarely by deletions involving KDM6A. Nearly one third of cases remain unsolved. Here, we expand the known genetic basis of KS by presenting five typical patients with the condition, all of whom have novel MLL2 mutation types-two patients with mosaic small deletions, one with a mosaic whole-gene deletion, one with a multi-exon deletion and one with an intragenic multi-exon duplication. We recommend MLL2 dosage studies for all patients with typical KS, where traditional Sanger sequencing fails to identify mutations. The prevalence of such MLL2 mutations in KS may be comparable with deletions involving KDM6A. These findings may be helpful in understanding the mutational mechanism of MLL2 and the disease mechanism of KS.