Limb disordersGene: SFRP4
Genomics England clinical team - Agree with green rating, mostly limb
Created: 9 Sep 2018, 5:55 p.m.
Comment on phenotypes: added synonym
Created: 6 Apr 2018, 1:01 p.m.
Comment on publications: added PMID 28100910 further evidence to support gene-phenotype which reports a 11-year-old female with PYL, and found a novel homozygous nonsense variant, c.183C>G (p.Y61*). Segregation analysis in the patient revealed a germline mutation, resulting in reduced protein formation. This is the second report from a fourth affected family with a SFRP4 mutation causing PYL disease.
Created: 6 Apr 2018, 12:56 p.m.
Comment on list classification: PMID:27355534 - A brother and sister with Pyle disease were homozygous for a frameshift variant in this gene, with unaffected parents and brother heterozygous. An additional two unrelated cases with loss of function variants are reported, however without evidence of segregation. These variants were identified with a variant filtering pipeline for rare variants. Features similar to Pyle disease were observed in knockout mice. Treatment of Sfrp4-deficient mice with a soluble Bmp2 receptor (RAP-661) or with antibodies to sclerostin corrected the cortical-bone defect. Other publications contribute evidence towards the role of this gene in bone density, skeletal development and the Wnt signalling pathway.
Created: 6 Apr 2018, 12:50 p.m.
Ellen McDonagh: Comment on list classification
This gene has been classified as Green List (High Evidence).
Phenotypes for SFRP4 were set to Pyle disease, 265900; PYL; Metaphyseal dysplasia
Phenotypes for SFRP4 were set to Pyle disease, 265900; PYL
Phenotypes for SFRP4 were set to Pyle disease, 265900
Publications for SFRP4 were set to 27355534; 27117872; 24096177; 26273529; 22965941; 22387305; 20174869; 27117872; 28100910
This gene has been classified as Amber List (Moderate Evidence).
SFRP4 was added to Limb disorders panel. Sources: Literature
SFRP4 was created by Ellen McDonagh