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

P. Makrythanasis, B. W. van Bon, M. Steehouwer, B. Rodríguez-Santiago, M. Simpson, P. Dias, B. M. Anderlid, P. Arts, M. Bhat, B. Augello, E. Biamino, E. M H F Bongers, M. del Campo, I. Cordeiro, A. M. Cueto-González, I. Cuscó, C. Deshpande, E. Frysira, L. Izatt, R. FloresE. Galán, B. Gener, C. Gilissen, S. M. Granneman, J. Hoyer, H. G. Yntema, C. M. Kets, D. A. Koolen, C. L. Marcelis, A. Medeira, L. Micale, S. Mohammed, S. A. de Munnik, A. Nordgren, S. Psoni, W. Reardon, N. Revencu, T. Roscioli, M. Ruiterkamp-Versteeg, H. G. Santos, J. Schoumans, J. H M Schuurs-Hoeijmakers, M. C. Silengo, L. Toledo, T. Vendrell, I. van der Burgt, B. van Lier, C. Zweier, A. Reymond, R. C. Trembath, L. Perez-Jurado, J. Dupont, B. B A de Vries, H. G. Brunner, J. A. Veltman, G. Merla, S. E. Antonarakis, A. Hoischen

Research output: Contribution to journalArticlepeer-review


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

Original languageEnglish
Pages (from-to)539-545
Number of pages7
JournalClinical Genetics
Issue number6
Publication statusPublished - Dec 2013


  • Genotype-phenotype correlation
  • Kabuki syndrome
  • MLL2
  • Niikawa-Kuroki syndrome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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