Mutation spectrum of MLL2 in a cohort of Kabuki syndrome patients.

TítuloMutation spectrum of MLL2 in a cohort of Kabuki syndrome patients.
Tipo de PublicaciónJournal Article
Nuevas Publicaciones2011
AutoresMicale L, Augello B, Fusco C, Selicorni A, Loviglio MN, Silengo MC, Reymond A, Gumiero B, Zucchetti F, D'Addetta EV, Belligni E, Calcagnì A, Digilio MC, Dallapiccola B, Faravelli F, Forzano F, Accadia M, Bonfante A, Clementi M, Daolio C, Douzgou S, Ferrari P, Fischetto R, Garavelli L, Lapi E, Mattina T, Melis D, Patricelli MG, Priolo M, Prontera P, Renieri A, Mencarelli MA, Scarano G, della Monica M, Toschi B, Turolla L, Vancini A, Zatterale A, Gabrielli O, Zelante L, Merla G
JournalOrphanet journal of rare diseases
Volumen6
Pagination38
Año de publicación2011
ISBN1750-1172
Resumen

BACKGROUND: Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenitali anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, viscerali and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histonei methyl transferase MLL2 genei 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-phenotypei correlations and improve clinical management.

DOI10.1186/1750-1172-6-38
Alternate JournalOrphanet J Rare Dis
Citation Key935
PubMed ID21658225