A mutation screen in patients with Kabuki syndrome

Yun Li, Nina Bögershausen, Yasemin Alanay, Pelin Özlem Simsek Kiper, Nadine Plume, Katharina Keupp, Esther Pohl, Barbara Pawlik, Martin Rachwalski, Esther Milz, Michaela Thoenes, Beate Albrecht, Eva Christina Prott, Margret Lehmkühler, Stephanie Demuth, Gülen Eda Utine, Koray Boduroglu, Katja Frankenbusch, Guntram Borck, Gabriele Gillessen-KaesbachGökhan Yigit, Dagmar Wieczorek, Bernd Wollnik*

*Corresponding author for this work
59 Citations (Scopus)


Kabuki syndrome (KS) is one of the classical, clinically well-known multiple anomalies/mental retardation syndromes, mainly characterized by a very distinctive facial appearance in combination with additional clinical signs such as developmental delay, short stature, persistent fingerpads, and urogenital tract anomalies. In our study, we sequenced all 54 coding exons of the recently identified MLL2 gene in 34 patients with Kabuki syndrome. We identified 18 distinct mutations in 19 patients, 11 of 12 tested de novo. Mutations were located all over the gene and included three nonsense mutations, two splice-site mutations, six small deletions or insertions, and seven missense mutations. We compared frequencies of clinical symptoms in MLL2 mutation carriers versus non-carriers. MLL2 mutation carriers significantly more often presented with short stature and renal anomalies (p = 0.026 and 0.031, respectively), and in addition, MLL2 carriers obviously showed more frequently a typical facial gestalt (17/19) compared with non-carriers (9/15), although this result was not statistically significant (p = 0.1). Mutation-negative patients were subsequently tested for mutations in ten functional candidate genes (e.g. MLL, ASC2, ASH2L, and WDR5), but no convincing causative mutations could be found. Our results indicate that MLL2 is the major gene for Kabuki syndrome with a wide spectrum of de novo mutations and strongly suggest further genetic heterogeneity.

Original languageEnglish
JournalHuman Genetics
Issue number6
Pages (from-to)715-724
Number of pages10
Publication statusPublished - 01.12.2011


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