Skeletal dysplasia

Gene: SFRP4

Green List (high evidence)

Pyle disease is characterized by long bones with wide and expanded trabecular metaphyses, thin cortical bone, and bone fragility. >3 cases reported; Review on behalf of Tracy Lester

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pyle disease 265900; PYL; Metaphyseal dysplasia

Publications

• 27355534
• 28100910
• 27117872
• 24096177
• 26273529
• 22965941
• 22387305
• 20174869
• 27117872

I don't know

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: SFRP4; Initial rating suggestion: green if SD

Created: 6 Mar 2019, 11:37 a.m.

Comment on list classification: Additional case reported in PMID 28100910, and internal clinical review confirmed that this gene should be promoted to green.

Created: 6 Apr 2018, 2:10 p.m.

Comment on publications: Other publications contribute evidence towards the role of this gene in bone density, skeletal development and the Wnt signalling pathway.

Created: 6 Apr 2018, 12:35 p.m.

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.

Created: 6 Apr 2018, 12:16 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pyle disease 265900

Publications

• 27355534