Multiple congenital malformations of Wolf-Hirschhorn syndrome are recapitulated in Fgfrl1 null mice.

[wolf-hirschhorn syndrome]

Wolf-Hirschhorn syndrome (WHS ) is caused by deletions in the short arm of chromosome 4 (4 p ) and occurs in about one per 20 ,000 births . Patients with WHS display a set of highly variable characteristics including craniofacial dysgenesis , mental retardation , speech problems , congenital heart defects , short stature and a variety of skeletal anomalies . Analysis of patients with 4 p deletions has identified two WHS critical regions (WHSCRs ); however , deletions targeting mouse WHSCRs do not recapitulate the classical WHS defects , and the genes contributing to WHS have not been conclusively established . Recently , the human FGFRL 1 gene , encoding a putative fibroblast growth factor (FGF ) decoy receptor , has been implicated in the craniofacial phenotype of a WHS patient . Here , we report that targeted deletion of the mouse Fgfrl 1 gene recapitulates a broad array of WHS phenotypes , including abnormal craniofacial development , axial and appendicular skeletal anomalies , and congenital heart defects . Fgfrl 1 null mutants also display a transient foetal anaemia and a fully penetrant diaphragm defect , causing prenatal and perinatal lethality . Together , these data support a wider role for Fgfrl 1 in development , implicate FGFRL 1 insufficiency in WHS , and provide a novel animal model to dissect the complex aetiology of this human disease .

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