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Clin Genet. 2013 Dec;84(6):539-45. doi: 10.1111/cge.12081. Epub 2013 Apr 26.

MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.

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  • 1Departement of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.

Abstract

Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p < 0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients.

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

KEYWORDS:

Kabuki syndrome; MLL2; Niikawa-Kuroki syndrome; genotype-phenotype correlation

PMID:
23320472
[PubMed - in process]
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