Clin Genet. 2013 Jan 16. doi: 10.1111/cge.12081. [Epub ahead of print]
Departement of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
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 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 to 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 4 splice-site mutations, 34 of which were novel. In 5 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-value <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.
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