title: A mutation screen in patients with Kabuki syndrome.
abstract: 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.
authors: Institute of Human Genetics and Center for Molecular Medicine Cologne, University Medical Faculty, University of Cologne, Kerpener Str. 34, 50931 Cologne, Germany.
authors: Yun
authors: Y
authors: Li
authors: Nina
authors: N
authors: Bögershausen
authors: Yasemin
authors: Y
authors: Alanay
authors: Pelin Ozlem
authors: PO
authors: Simsek Kiper
authors: Nadine
authors: N
authors: Plume
authors: Katharina
authors: K
authors: Keupp
authors: Esther
authors: E
authors: Pohl
authors: Barbara
authors: B
authors: Pawlik
authors: Martin
authors: M
authors: Rachwalski
authors: Esther
authors: E
authors: Milz
authors: Michaela
authors: M
authors: Thoenes
authors: Beate
authors: B
authors: Albrecht
authors: Eva-Christina
authors: EC
authors: Prott
authors: Margret
authors: M
authors: Lehmkühler
authors: Stephanie
authors: S
authors: Demuth
authors: Gülen Eda
authors: GE
authors: Utine
authors: Koray
authors: K
authors: Boduroglu
authors: Katja
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authors: Frankenbusch
authors: Guntram
authors: G
authors: Borck
authors: Gabriele
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authors: Gillessen-Kaesbach
authors: Gökhan
authors: G
authors: Yigit
authors: Dagmar
authors: D
authors: Wieczorek
authors: Bernd
authors: B
authors: Wollnik
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