Skeletal dysplasia

Gene: FZD2

Green List (high evidence)

Mesomelic and rhizo-mesomelic dysplasias gp of SD - >3 cases reported. Robinow-like phenotype.; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Autosomal dominant omodysplasia type 2 164745

Publications

• 25759469
• 29230162
• 29383830
• 29383834
• 30455931

I don't know

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 cases

Created: 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: Green

Created: 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.

Green List (high evidence)

Tier 1

Created: 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