Individuals with heterozygous variants in the Wnt-signalling pathway gene FZD5 delineate a phenotype characterized by isolated coloboma and variable expressivity

Richard Holt, David Goudie, Alejandra Damián Verde, Alice Gardham, Francis Ramond, Audrey Putoux, Ajoy Sarkar, Virginia Clowes, Jill Clayton-Smith, Siddharth Banka, Laura Cortazar Galarza, Gilles Thuret, Marta Ubeda Erviti, Ane Zurutuza Ibarguren, Raquel Sáez Villaverde, Alejandra Tamayo Durán, Carmen Ayuso, Dorine A. Bax, Julie Plaisancie, Marta CortonNicolas Chassaing, Patrick Calvas, Nicola K. Ragge (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
43 Downloads (Pure)

Abstract

Background: Anophthalmia, microphthalmia and coloboma are a genetically heterogenous spectrum of developmental eye disorders. Recently, variants in the Wnt-pathway gene Frizzled Class Receptor 5 (FZD5) have been identified in individuals with coloboma and rarely microphthalmia, sometimes with additional phenotypes and variable penetrance.

Materials and Methods: We identified variants in FZD5 in individuals with developmental eye disorders from the UK (including the DDD Study [www.ddduk.org/access.html]), France and Spain using whole genome/exome sequencing or customized NGS panels of ocular development genes.

Results: We report eight new families with FZD5 variants and ocular coloboma. Three individuals presented with additional syndromic features, two explicable by additional variants in other genes (SLC12A2 and DDX3X). In two families initially showing incomplete penetrance, re-examination of apparently unaffected carrier individuals revealed subtle ocular colobomatous phenotypes. Finally, we report two families with microphthalmia in addition to coloboma, representing the second and third reported cases of this phenotype in conjunction with FZD5 variants.

Conclusions: Our findings indicate FZD5 variants are typically associated with isolated ocular coloboma, occasionally microphthalmia, and that extraocular phenotypes are likely to be explained by other gene alterations.

Original languageEnglish
Pages (from-to)809-816
Number of pages8
JournalOphthalmic Genetics
Volume43
Issue number6
DOIs
Publication statusPublished - 25 Jan 2023

Keywords

  • coloboma
  • FZD5
  • genetic testing
  • microphthalmia
  • patient care
  • penetrance
  • Wnt signalling pathway

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Ophthalmology
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'Individuals with heterozygous variants in the Wnt-signalling pathway gene FZD5 delineate a phenotype characterized by isolated coloboma and variable expressivity'. Together they form a unique fingerprint.

Cite this