MLL2 mosaic mutations and intragenic deletion–duplications in patients with Kabuki syndrome. (18th September 2012)

• Record Type: Journal Article
• Authors: Banka, S; Howard, E; Bunstone, S; Chandler, KE; Kerr, B; Lachlan, K; McKee, S; Mehta, SG; Tavares, ALT; Tolmie, J; Donnai, D
• Is Part Of: Clinical genetics. Volume 83:Number 5(2013:May)
• Page Start: 467
• Page End: 471
• Publication Date: 2012-09-18
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/j.1399-0004.2012.01955.x
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>MLL2</italic> point mutations in the majority of the cases and, rarely by deletions involving <italic>KDM6A</italic>. 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 <italic>MLL2</italic> 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 <italic>MLL2</italic> dosage studies for all patients with typical KS, where traditional Sanger sequencing fails to identify mutations. The prevalence of such <italic>MLL2</italic> mutations in KS may be comparable with deletions involving <italic>KDM6A</italic>. These findings may be helpful in understanding the mutational mechanism of <italic>MLL2</italic> and the disease mechanism of KS.</p> </abstract>