CHARGE and Kabuki syndromes: a phenotypic and molecular link.

[kabuki syndrome]

CHARGE syndrome is a complex developmental disorder caused by mutations in the chromodomain helicase DNA-binding gene CHD 7 . Kabuki syndrome , another developmental disorder , is characterized by typical facial features in combination with developmental delay , short stature , prominent digit pads and visceral abnormalities . Mutations in the KMT 2 D gene , which encodes a H 3 K 4 histone methyltransferase , are the major cause of Kabuki syndrome . Here , we report a patient , who was initially diagnosed with CHARGE syndrome based on the spectrum of inner organ malformations like choanal hypoplasia , heart defect , anal atresia , vision problems and conductive hearing impairment . While sequencing and MLPA analysis of all coding exons of CHD 7 revealed no pathogenic mutation , sequence analysis of the KMT 2 D gene identified the heterozygous de novo nonsense mutation c .5263 C > T (p .Gln 1755 *). Thus , our patient was diagnosed with Kabuki syndrome . By using co -immunoprecipitation , immunohistochemistry and direct yeast two hybrid assays , we could show that , like KMT 2 D , CHD 7 interacts with members of the WAR complex , namely WDR 5 , ASH 2 L and RbBP 5 . We therefore propose that CHD 7 and KMT 2 D function in the same chromatin modification machinery , thus pointing out a mechanistic connection , and presenting a probable explanation for the phenotypic overlap between Kabuki and CHARGE syndromes .

Diseases
Validation

Diseases presenting "short stature" symptom

22q11.2 deletion syndrome

achondroplasia

alpha-thalassemia

aromatase deficiency

child syndrome

classical phenylketonuria

coats disease

cohen syndrome

congenital adrenal hyperplasia

cowden syndrome

dentin dysplasia

dentinogenesis imperfecta

fabry disease

hirschsprung disease

holt-oram syndrome

kabuki syndrome

kallmann syndrome

kindler syndrome

monosomy 21

oculocutaneous albinism

oligodontia

omenn syndrome

proteus syndrome

werner syndrome

wolf-hirschhorn syndrome

zellweger syndrome

This symptom has already been validated