Abstract
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.
Highlights
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
Kabuki syndrome (KS, MIM #147920), known as Niikawa-Kuroki syndrome, is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, which is defined by long palpebral fissures with eversion of the lateral third of the lower eyelids, short columella with a broad and depressed nasal
Exome sequencing recently revealed that mutations in the histone methyltransferase MLL2 gene are a major cause of Kabuki syndrome [6]
Summary
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. Kabuki syndrome (KS, MIM #147920), known as Niikawa-Kuroki syndrome, is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, which is defined by long palpebral fissures with eversion of the lateral third of the lower eyelids, short columella with a broad and depressed nasal family of histone methyl transferases (HMT). The highly conserved SET domain of MLLs confers histone methyltransferase activity, which is the core function of HMTs. MLLs are important in the epigenetic control of active chromatin states [9]. MLLs are important in the epigenetic control of active chromatin states [9] They act as transcriptional co-activators and are involved in embryogenesis and development through, for example, regulation of the expression of the HOX genes and their interaction with nuclear receptors [10,11]. MLL2 is involved in estrogen receptor a (ERa)mediated signal transduction, acting as a coactivator of a complex that includes ASH2, RBQ3, and WDR5 [14]
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