dc.contributor.author | Hoem, Gry | |
dc.contributor.author | Pastore, Arianna | |
dc.contributor.author | Bratland, Eirik | |
dc.contributor.author | Christoffersen, Terje | |
dc.contributor.author | Stornaiuolo, Mariano | |
dc.contributor.author | Houge, Sofia Douzgou | |
dc.date.accessioned | 2024-10-10T09:39:30Z | |
dc.date.available | 2024-10-10T09:39:30Z | |
dc.date.issued | 2024-02-15 | |
dc.description.abstract | Familial exudative vitreoretinopathy (FEVR) is linked to disruption of the Norrin/
Frizzled-4 signaling pathway, which plays an important role in retinal angiogenesis.
Severe or complete knock-down of proteins in the pathway also causes syndromic
forms of the condition. Both heterozygous and biallelic pathogenic variants in the
FZD4 gene, encoding the pathway's key protein frizzled-4, are known to cause FEVR.
However, it is not clear what effect different FZD4 variants have, and whether
extraocular features should be expected in those with biallelic pathogenic FZD4 variants. Biallelic FZD4 variants were found in a young boy with isolated, severe FEVR.
His parents were heterozygous for one variant each and reported normal vision. Invitro studies of the two variants, demonstrated that it was the combination of the
two which led to severe inhibition of the Norrin/Frizzled-4 pathway. Our observations demonstrate that biallelic FZD4-variants are associated with a severe form of
FEVR, which does not necessarily include extraocular features. In addition, variants
causing severe FEVR in combination, may have no or minimal effect in heterozygous
parents as non-penetrance is also a major feature in dominant FZD4-FEVR disease.
This underscores the importance of genetic testing of individuals and families
with FEVR. | en_US |
dc.identifier.citation | Hoem, Pastore, Bratland, Christoffersen, Stornaiuolo, Houge. Severe isolated exudative vitreoretinopathy caused by biallelic FZD4 variants. Clinical Genetics. 2024 | en_US |
dc.identifier.cristinID | FRIDAID 2258201 | |
dc.identifier.doi | 10.1111/cge.14499 | |
dc.identifier.issn | 0009-9163 | |
dc.identifier.issn | 1399-0004 | |
dc.identifier.uri | https://hdl.handle.net/10037/35177 | |
dc.language.iso | eng | en_US |
dc.publisher | Wiley | en_US |
dc.relation.journal | Clinical Genetics | |
dc.rights.accessRights | openAccess | en_US |
dc.rights.holder | Copyright 2024 The Author(s) | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | en_US |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) | en_US |
dc.title | Severe isolated exudative vitreoretinopathy caused by biallelic FZD4 variants | en_US |
dc.type.version | publishedVersion | en_US |
dc.type | Journal article | en_US |
dc.type | Tidsskriftartikkel | en_US |
dc.type | Peer reviewed | en_US |