Mutations in osteoprotegerin account for the CCAL1 locus in calcium pyrophosphate deposition disease.

ABSTRACT: OBJECTIVE:Mutations on chromosomes 5p (CCAL2) and 8q (CCAL1) have been linked to familial forms of calcium pyrophosphate deposition disease (CPDD). Mutations in the ANKH gene account for CCAL2, but the identity of CCAL1 has been elusive. Recently, a single Dutch kindred with a mutation in the Tumor Necrosis Factor Receptor Super Family member 11B (TNFRSF11B) gene coding for osteoprotegerin (OPG) was described as a gain-of-function mutation. Affected family members had premature generalized osteoarthritis (PGOA) and CPDD. As the TNFRSF11B gene is on 8q, we sought additional evidence that TNFRSF11B was CCAL1, and investigated potential disease mechanisms. DESIGN:DNA from two novel PGOA/CPDD families was screened for sequence variants in the TNFRSF11B gene. Mutations were verified by genotype

SUBMITTER: Williams CJ 

PROVIDER: S-EPMC6293976 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature