Submission Details

Autosomal recessive

12/05/2019

The PRG4 gene is located on chromosome 1 at 1q31.1 and encodes the proteoglycan 4 protein, which is lubricating component of the synovial fluid and acts as a boundary lubricant at the cartilage surface. It also has a chondroprotective feature and acts by preventing protein deposition from the synovial fluid onto the cartilage surface. PRG4 was first reported in relation to autosomal recessive, camptodactyly-arthropathy-coxa vara-pericarditis syndrome in 1999 (10545950: Marcelino et al. 1999). At least seven unique loss of function variants have been reported in literature. Evidence supporting this gene-disease relationship includes case-level data, segregation data, experimental data. Variants in this gene have been reported in at least six probands from three publications (10545950: Marcelino et al. 1999; 27224999: Peters et al. 2016; 29397575: Yilmaz et al. 2018). Variants in this gene segregated with disease in three families. One of the families reported 12 affected family members, five of whom were genotyped. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. Homozygous loss of function is implicated as the mechanism of disease. This gene-disease association is supported by expression studies and two independent Prg4 -/- mouse modes that recapitulate the human disease (10545950: Marcelino et al. 1999; 15719068: Rhee et al. 2005; 20191580: Coles et al. 2010). In summary, PRG4 is definitively associated with autosomal recessive, camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

10545950 27224999 29397575 20191580 15719068