A mutation screen in patients with Kabuki syndrome.

[kabuki syndrome]

Kabuki syndrome (KS ) is one of the classical , clinically well-known multiple anomalies /mental retardation syndromes , mainly characterized by a very distinctive facial appearance in combination with additional clinical signs such as developmental delay , short stature , persistent fingerpads , and urogenital tract anomalies . In our study , we sequenced all 54 coding exons of the recently identified MLL 2 gene in 34 patients with Kabuki syndrome . We identified 18 distinct mutations in 19 patients , 11 of 12 tested de novo . Mutations were located all over the gene and included three nonsense mutations , two splice-site mutations , six small deletions or insertions , and seven missense mutations . We compared frequencies of clinical symptoms in MLL 2 mutation carriers versus non-carriers . MLL 2 mutation carriers significantly more often presented with short stature and renal anomalies (p Â =Â 0 .026 and 0 .031 , respectively ), and in addition , MLL 2 carriers obviously showed more frequently a typical facial gestalt (17 /19 ) compared with non-carriers (9 /15 ), although this result was not statistically significant (p Â =Â 0 .1 ). Mutation-negative patients were subsequently tested for mutations in ten functional candidate genes (e .g . MLL , ASC 2 , ASH 2 L , and WDR 5 ), but no convincing causative mutations could be found . Our results indicate that MLL 2 is the major gene for Kabuki syndrome with a wide spectrum of de novo mutations and strongly suggest further genetic heterogeneity .

Diseases
Validation

Diseases presenting "mental retardation" symptom

achondroplasia

alexander disease

alpha-thalassemia

aniridia

aromatase deficiency

canavan disease

classical phenylketonuria

coats disease

cohen syndrome

cowden syndrome

cystinuria

dentin dysplasia

familial hypocalciuric hypercalcemia

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

kabuki syndrome

kallmann syndrome

lamellar ichthyosis

lymphangioleiomyomatosis

monosomy 21

phenylketonuria

primary hyperoxaluria type 1

proteus syndrome

pyruvate dehydrogenase deficiency

sneddon syndrome

triple a syndrome

wolf-hirschhorn syndrome

zellweger syndrome

This symptom has already been validated