RGD Reference Report - Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy. - Rat Genome Database

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Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.

Authors: Robitaille, J  MacDonald, ML  Kaykas, A  Sheldahl, LC  Zeisler, J  Dube, MP  Zhang, LH  Singaraja, RR  Guernsey, DL  Zheng, B  Siebert, LF  Hoskin-Mott, A  Trese, MT  Pimstone, SN  Shastry, BS  Moon, RT  Hayden, MR  Goldberg, YP  Samuels, ME 
Citation: Robitaille J, etal., Nat Genet. 2002 Oct;32(2):326-30. Epub 2002 Aug 12.
RGD ID: 1598999
Pubmed: PMID:12172548   (View Abstract at PubMed)
DOI: DOI:10.1038/ng957   (Journal Full-text)

Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Loci associated with FEVR map to 11q13-q23 (EVR1; OMIM 133780, ref. 1), Xp11.4 (EVR2; OMIM 305390, ref. 2) and 11p13-12 (EVR3; OMIM 605750, ref. 3). Here we have confirmed linkage to the 11q13-23 locus for autosomal dominant FEVR in one large multigenerational family and refined the disease locus to a genomic region spanning 1.55 Mb. Mutations in FZD4, encoding the putative Wnt receptor frizzled-4, segregated completely with affected individuals in the family and were detected in affected individuals from an additional unrelated family, but not in normal controls. FZD genes encode Wnt receptors, which are implicated in development and carcinogenesis. Injection of wildtype and mutated FZD4 into Xenopus laevis embryos revealed that wildtype, but not mutant, frizzled-4 activated calcium/calmodulin-dependent protein kinase II (CAMKII) and protein kinase C (PKC), components of the Wnt/Ca(2+) signaling pathway. In one of the mutants, altered subcellular trafficking led to defective signaling. These findings support a function for frizzled-4 in retinal angiogenesis and establish the first association between a Wnt receptor and human disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
exudative vitreoretinopathy 1  IAGP 1598999 RGD 
exudative vitreoretinopathy 1  ISOFZD4 (Homo sapiens)1598999; 1598999 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fzd4  (frizzled class receptor 4)

Genes (Mus musculus)
Fzd4  (frizzled class receptor 4)

Genes (Homo sapiens)
FZD4  (frizzled class receptor 4)


Additional Information