MLL2 mutation spectrum in 45 patients with Kabuki syndrome.

[kabuki syndrome]

Kabuki Syndrome (KS ) is a rare syndrome characterized by intellectual disability and multiple congenital abnormalities , in particular a distinct dysmorphic facial appearance . KS is caused by mutations in the MLL 2 gene , encoding an H 3 K 4 histone methyl transferase which acts as an epigenetic transcriptional activator during growth and development . Direct sequencing of all 54 exons of the MLL 2 gene in 45 clinically well-defined KS patients identified 34 (75 .6 %) different mutations . One mutation has been described previously , all others are novel . Clinically , all KS patients were sporadic , and mutations were de novo for all 27 families for which both parents were available . We detected nonsense (n =11 ), frameshift (n =17 ), splice site (n =4 ) and missense (n =2 ) mutations , predicting a high frequency of absent or non-functional MLL 2 protein . Interestingly , both missense mutations located in the C-terminal conserved functional domains of the protein . Phenotypically our study indicated a statistically significant difference in the presence of a distinct facial appearance (p =0 .0143 ) and growth retardation (p =0 .0040 ) when comparing KS patients with an MLL 2 mutation compared to patients without a mutation . Our data double the number of MLL 2 mutations in KS reported so far and widen the spectrum of MLL 2 mutations and disease mechanisms in KS .

Diseases
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Diseases presenting "distinct dysmorphic facial appearance" symptom

kabuki syndrome

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