Skeletal dysplasia
Gene: FZD2
Mesomelic and rhizo-mesomelic dysplasias gp of SD - >3 cases reported. Robinow-like phenotype.; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Autosomal dominant omodysplasia type 2 164745
Publications
Comment on list classification: More than 3 cases with variants in FZD2 in patients with a relevant phenotype.Created: 17 Jul 2019, 11:23 a.m. | Last Modified: 17 Jul 2019, 11:23 a.m.
Panel Version: 1.177
Associated with Omodysplasia 2 (164745) in OMIM.
PMID: 25759469 - Saal et al 2015 - 1 family. proband with omodysplasia, her unaffected parents and her affected daughter. Identified a de novo mutation (c.1644G>A, p.Trp548*) in FZD2 in the proband and her daughter that was not found in unaffected family members. Show reduced ability of this mutant form of FZD2 to interact with its downstream target DISHEVELLED. Furthermore, expressing the mutant form of FZD2 in vitro is not able to facilitate the cellular response to canonical Wnt signaling like wild-type FZD2.
PMID: 29230162 - Türkmen et al 2017 - 1 patient. A heterozygous de novo mutation (G434V) in the frizzled class receptor 2 (FZD2) gene in a patient with distinct facial features including hypertelorism, bilateral cleft lip/palate, short nose with a broad nasal bridge, microretrognathia, and bilateral shortness of the upper limbs, first metacarpal bones, and middle phalanges of the 5th digits.
PMID: 29383830 - invalid pubmed id
PMID: 29383834 - Nagasaki et al 2018 - 1 patient. 16-year-old boy with OMOD2 or Robinow syndrome-like phenotype. Molecular analysis identified a de novo, heterozygous, nonsense mutation (c.1640C>A, p.S547*) in FZD2.
PMID: 30455931 - Warren et al 2018 - 2 patients. Presented are two patients with autosomal dominant omodysplasia and mutations in the FZD2 gene. Patient 1 has a p.Trp548* alteration previously reported. Patient 2 has missense alteration p.Gly434Val also previously reported. The phenotypes of these patients overlap with what has been previously reported, though patient 2 also presented with intellectual disability which is not typical.
Total of 4 casesCreated: 8 May 2019, 2:24 p.m. | Last Modified: 17 Jul 2019, 11:22 a.m.
Panel Version: 1.176
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: FZD2; Initial rating suggestion: GreenCreated: 6 Mar 2019, 11:36 a.m.
Comment when marking as ready: Not associated with phenotype in OMIM nor G2P. Single variant reported (2015)Created: 28 Jul 2016, 12:26 p.m.
Tier 1Created: 17 Jun 2016, 8:04 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Autosomal dominant omodysplasia 164745
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: FZD2 were changed from Autosomal dominant omodysplasia type 2 164745; Autosomal dominant omodysplasia 164745 to Omodysplasia 2, OMIM:164745; Robinow syndrome
Gene: fzd2 has been classified as Green List (High Evidence).
Added phenotypes Autosomal dominant omodysplasia type 2 164745 for gene: FZD2 Publications for gene FZD2 were changed from 25759469 to 29230162; 30455931; 29383834; 29383830; 25759469
Source NHS GMS was added to FZD2.
Promoted to version 1 9th August 2016
This gene has been classified as Red List (Low Evidence).
Mode of inheritance for FZD2 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for FZD2 were set to Autosomal dominant omodysplasia 164745
Publications for FZD2 were set to 25759469
FZD2 was added to Unexplained skeletal dysplasiapanel. Sources:
FZD2 was created by sleigh