A mutation screen in patients with Kabuki syndrome

作者：Li Yun; Boegershausen Nina; Alanay Yasemin; Kiper Pelin Ozlem Simsek; Plume Nadine; Keupp Katharina; Pohl Esther; Pawlik Barbara; Rachwalski Martin; Milz Esther; Thoenes Michaela; Albrecht Beate; Prott Eva Christina; Lehmkuehler Margret; Demuth Stephanie; Utine Gulen Eda; Boduroglu Koray; Frankenbusch Katja; Borck Guntram; Gillessen Kae**ach Gabriele; Yigit Gokhan; Wieczorek Dagmar; Wollnik Bernd^*

来源：Human Genetics, 2011, 130(6): 715-724.

DOI：10.1007/s00439-011-1004-y

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.

• 出版日期2011-12