Mutation spectrum of MLL2 in a cohort of kabuki syndrome patients

Lucia Micale, Bartolomeo Augello, Carmela Fusco, Angelo Selicorni, Maria N. Loviglio, Margherita Cirillo Silengo, Alexandre Reymond, Barbara Gumiero, Federica Zucchetti, Ester V. D'Addetta, Elga Belligni, Alessia Calcagn, Maria C. Digilio, Bruno Dallapiccola, Francesca Faravelli, Francesca Forzano, Maria Accadia, Aldo Bonfante, Maurizio Clementi, Cecilia DaolioSofia Douzgou, Paola Ferrari, Rita Fischetto, Livia Garavelli, Elisabetta Lapi, Teresa Mattina, Daniela Melis, Maria G. Patricelli, Manuela Priolo, Paolo Prontera, Alessandra Renieri, Maria A. Mencarelli, Gioacchino Scarano, Matteo Della Monica, Benedetta Toschi, Licia Turolla, Alessandra Vancini, Adriana Zatterale, Orazio Gabrielli, Leopoldo Zelante, Giuseppe Merla

Research output: Contribution to journalArticlepeer-review


Background: Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histone methyl transferase MLL2 gene have been identified as its underlying cause. Methods. Genomic DNAs were extracted from 62 index patients clinically diagnosed as affected by Kabuki syndrome. Sanger sequencing was performed to analyze the whole coding region of the MLL2 gene including intron-exon junctions. The putative causal and possible functional effect of each nucleotide variant identified was estimated by in silico prediction tools. Results: We identified 45 patients with MLL2 nucleotide variants. 38 out of the 42 variants were never described before. Consistently with previous reports, the majority are nonsense or frameshift mutations predicted to generate a truncated polypeptide. We also identified 3 indel, 7 missense and 3 splice site. Conclusions: This study emphasizes the relevance of mutational screening of the MLL2 gene among patients diagnosed with Kabuki syndrome. The identification of a large spectrum of MLL2 mutations possibly offers the opportunity to improve the actual knowledge on the clinical basis of this multiple congenital anomalies/mental retardation syndrome, design functional studies to understand the molecular mechanisms underlying this disease, establish genotype-phenotype correlations and improve clinical management.

Original languageEnglish
Article number38
JournalOrphanet Journal of Rare Diseases
Issue number1
Publication statusPublished - 2011

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

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