title: Mutation spectrum of MLL2 in a cohort of Kabuki syndrome patients.
abstract: 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.
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza Hospital, 71013 San Giovanni Rotondo, Italy.
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authors.lastname: Micale
authors.forename: Bartolomeo
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authors.lastname: Augello
authors.forename: Carmela
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authors.forename: Angelo
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authors.lastname: Selicorni
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authors.lastname: Loviglio
authors.forename: Margherita Cirillo
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authors.lastname: Reymond
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authors.forename: Aldo
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authors.forename: Maurizio
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authors.forename: Cecilia
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authors.forename: Sofia
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authors.forename: Paola
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authors.lastname: Ferrari
authors.forename: Rita
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authors.lastname: Fischetto
authors.forename: Livia
authors.initials: L
authors.lastname: Garavelli
authors.forename: Elisabetta
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authors.lastname: Lapi
authors.forename: Teresa
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authors.lastname: Mattina
authors.forename: Daniela
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authors.lastname: Melis
authors.forename: Maria G
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authors.lastname: Patricelli
authors.forename: Manuela
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authors.lastname: Priolo
authors.forename: Paolo
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authors.lastname: Prontera
authors.forename: Alessandra
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authors.lastname: Renieri
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mencarelli
authors.forename: Gioacchino
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authors.lastname: Scarano
authors.forename: Matteo
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authors.lastname: della Monica
authors.forename: Benedetta
authors.initials: B
authors.lastname: Toschi
authors.forename: Licia
authors.initials: L
authors.lastname: Turolla
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vancini
authors.forename: Adriana
authors.initials: A
authors.lastname: Zatterale
authors.forename: Orazio
authors.initials: O
authors.lastname: Gabrielli
authors.forename: Leopoldo
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authors.lastname: Zelante
authors.forename: Giuseppe
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authors.lastname: Merla
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics; D005145:Face / Q000002:abnormalities / Q000473:pathology; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D056726:Genetic Association Studies; D006402:Hematologic Diseases / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D017422:Sequence Analysis, DNA; D015837:Vestibular Diseases / Q000235:genetics* / Q000473:pathology*
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins