MLL2 mosaic mutations and intragenic deletion-duplications in patients with Kabuki syndrome

被引：47

作者：

Banka, S. ^{[1
]}

Howard, E. ^{[1
]}

Bunstone, S. ^{[1
]}

Chandler, K. E. ^{[1
]}

Kerr, B. ^{[1
]}

Lachlan, K. ^{[2
,3
]}

McKee, S. ^{[4
]}

Mehta, S. G. ^{[5
]}

Tavares, A. L. T. ^{[5
]}

Tolmie, J. ^{[6
]}

Donnai, D. ^{[1
]}

机构：

[1] Univ Manchester, St Marys Hosp, Manchester Acad Hlth Sci Ctr MAHSC, Dept Genet Med, Manchester M13 0JH, Lancs, England

[2] Univ Hosp Southampton NHS Trust & Human Genet & G, Wessex Clin Genet Serv, Southampton, Hants, England

[3] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England

[4] Belfast City Hosp, Northern Ireland Reg Genet Serv, Belfast BT9 7AD, Antrim, North Ireland

[5] Addenbrookes Hosp, Dept Clin Genet, East Anglian Med Genet Serv, Cambridge, England

[6] Yorkhill Hosp, Dept Clin Genet, Glasgow, Lanark, Scotland

来源：

CLINICAL GENETICS | 2013年 / 83卷 / 05期

关键词：

intragenic deletion duplication; Kabuki syndrome; KDM6A; MLL2; mosaic; SPECTRUM;

D O I：

10.1111/j.1399-0004.2012.01955.x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：467 / 471

页数：5

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