These authors contributed equally.
MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype–phenotype study
Article first published online: 26 APR 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 84, Issue 6, pages 539–545, December 2013
How to Cite
MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype–phenotype study., , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .
Nothing to declare.
- Issue published online: 28 OCT 2013
- Article first published online: 26 APR 2013
- Accepted manuscript online: 16 JAN 2013 04:15AM EST
- Manuscript Revised: 17 DEC 2012
- Manuscript Accepted: 17 DEC 2012
- Manuscript Received: 29 MAY 2012
- Netherlands Organization for Health Research and Development. Grant Numbers: 917-66-36, 911-08-025, 917-86-319, 916-12-095
- EU-funded TECHGENE project
- AnEUploidy project
- SNF and Gebert
- Australian NHMRC
- Bodossaki Foundation
- Swedish Medical Research Council
- genotype–phenotype correlation;
- Kabuki syndrome;
- Niikawa–Kuroki syndrome
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.