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
Validation

Diseases presenting "intellectual disability" symptom

22q11.2 deletion syndrome

alexander disease

alpha-thalassemia

aniridia

child syndrome

cohen syndrome

cowden syndrome

hirschsprung disease

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

kabuki syndrome

kallmann syndrome

monosomy 21

oculocutaneous albinism

oligodontia

phenylketonuria

proteus syndrome

triple a syndrome

wolf-hirschhorn syndrome

This symptom has already been validated