Mutation spectrum of MLL2 in a cohort of kabuki syndrome patientsReport as inadecuate

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Orphanet Journal of Rare Diseases

, 6:38

First Online: 09 June 2011Received: 11 March 2011Accepted: 09 June 2011DOI: 10.1186-1750-1172-6-38

Cite this article as: Micale, L., Augello, B., Fusco, C. et al. Orphanet J Rare Dis 2011 6: 38. doi:10.1186-1750-1172-6-38


BackgroundKabuki 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.

MethodsGenomic 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.

ResultsWe 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.

ConclusionsThis 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1750-1172-6-38 contains supplementary material, which is available to authorized users.

Lucia Micale, Bartolomeo Augello, Carmela Fusco, Leopoldo Zelante and Giuseppe Merla contributed equally to this work.

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Author: Lucia Micale - Bartolomeo Augello - Carmela Fusco - Angelo Selicorni - Maria N Loviglio - Margherita Cirillo Silengo - Ale


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