Document Detail

MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.
MedLine Citation:
PMID:  23320472     Owner:  NLM     Status:  Publisher    
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 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 to 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 4 splice-site mutations, 34 of which were novel. In 5 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-value <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.
Periklis Makrythanasis; Bregje W van Bon; Marloes Steehouwer; Benjamín Rodríguez-Santiago; Michael Simpson; Patricia Dias; Britt Marie Anderlid; Peer Arts; Meenakshi Bhat; Bartolomeo Augello; Elisa Biamino; Ernie Mhf Bongers; Miguel Del Campo; Isabel Cordeiro; Anna M Cueto-González; Ivon Cuscó; Charu Deshpande; Elena Frysira; Louise Izatt; Raquel Flores; Enrique Galán; Blanca Gener; Christian Gilissen; Susanne M Granneman; Juliane Hoyer; Helger G Yntema; C Marleen Kets; David A Koolen; Carlo L Marcelis; Ana Medeira; Lucia Micale; Shehla Mohammed; Sonja A de Munnik; Ann Nordgren; Stavroula Psoni15 Willie Reardon; Nicole Revencu; Tony Roscioli; Martina Ruiterkamp-Versteeg; Heloísa G Santos; Jacqueline Schoumans; Janneke Hm Schuurs-Hoeijmakers; Margherita Cirillo Silengo; Laura Toledo; Teresa Vendrell; Ineke van der Burgt; Bart van Lier; Christiane Zweier; Alexandre Reymond; Richard C Trembath; Luis Perez-Jurado; Juliette Dupont; Bert Ba de Vries; Han G Brunner; Joris A Veltman; Giuseppe Merla; Stylianos E Antonarakis; Alexander Hoischen
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-16
Journal Detail:
Title:  Clinical genetics     Volume:  -     ISSN:  1399-0004     ISO Abbreviation:  Clin. Genet.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0253664     Medline TA:  Clin Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 John Wiley & Sons A/S.
Departement of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
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