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 "growth factor" symptom

22q11.2 deletion syndrome

achondroplasia

adrenal incidentaloma

aniridia

cadasil

cholangiocarcinoma

coats disease

dedifferentiated liposarcoma

dentin dysplasia

dentinogenesis imperfecta

dystrophic epidermolysis bullosa

esophageal carcinoma

esophageal squamous cell carcinoma

hodgkin lymphoma, classical

holt-oram syndrome

inclusion body myositis

kallmann syndrome

krabbe disease

liposarcoma

lymphangioleiomyomatosis

oculocutaneous albinism

oral submucous fibrosis

pleomorphic liposarcoma

primary effusion lymphoma

primary hyperoxaluria type 1

severe combined immunodeficiency

systemic capillary leak syndrome

von hippel-lindau disease

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

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