A novel sequence variant in SFRP4 causing Pyle disease

Pyle disease (PYL) is an extremely rare disorder of irregular development of long bone. Recently, homozygous mutations in secreted frizzled-related protein 4 gene (SFRP4) gene were found to underlie this condition. Sequencing of coding regions of SFRP4 gene from an 11-year-old female with PYL was performed. A novel homozygous nonsense variant, c.183C>G (p.Y61∗) was observed. 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.