Genotype-phenotype investigation of 35 patients from 11 unrelated families with camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome.

TitleGenotype-phenotype investigation of 35 patients from 11 unrelated families with camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome.
Publication TypeJournal Article
Year of Publication2018
AuthorsYilmaz, S, Alkaya, DUludağ, Kasapcopur, O, Barut, K, Akdemir, ES, Celen, C, Youngblood, MW, Yasuno, K, Bilguvar, K, Günel, M, Tuysuz, B
JournalMol Genet Genomic Med
Date Published2018 03
KeywordsAdolescent, Adult, Arthropathy, Neurogenic, Child, Child, Preschool, Coxa Vara, Exons, Female, Genetic Association Studies, Hand Deformities, Congenital, Humans, Male, Middle Aged, Mutation, Proteoglycans, Retrospective Studies, Sequence Deletion, Synovitis, Whole Exome Sequencing

BACKGROUND: The camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is a rare autosomal recessive condition characterized by camptodactyly, noninflammatory arthropathy, coxa vara, and pericarditis. CACP is caused by mutations in the proteoglycan 4 (PRG4) gene, which encodes a lubricating glycoprotein present in the synovial fluid and at the surface of articular cartilage.

METHODS: In the present study, we compared the clinical and molecular findings of CACP syndrome in 35 patients from 11 unrelated families. In 28 patients, whole exome sequencing was used to investigate genomic variations.

RESULTS: We found that camptodactyly of hands was the first symptom presented by most patients. Swelling of wrists, knees, and elbows began before 4 years of age, while the age of joint involvement was variable. Patients reported an increased pain level after the age of 10, and severe hip involvement developed after 20 years old. All patients presented developmental coxa vara and seven patients (~22%) had pleural effusion, pericarditis, and/or ascites. We identified nine novel genomic alterations, including the first case of homozygous complete deletion of exon 1 in the PRG4 gene.

CONCLUSION: With this study, we contribute to the catalog of CACP causing variants. We confirm that the skeletal component of this disease worsens with age, and presents the potential mechanisms for interfamily variability, by discussing the influence of a modifier gene and escape from nonsense-mediated mRNA decay. We believe that this report will increase awareness of this familial arthropathic condition and the characteristic clinical and radiological findings will facilitate the differentiation from the common childhood rheumatic diseases such as juvenile idiopathic arthritis.

Alternate JournalMol Genet Genomic Med
PubMed ID29397575
PubMed Central IDPMC5902402
Grant ListS10 OD018521 / OD / NIH HHS / United States
T32 GM007205 / GM / NIGMS NIH HHS / United States
UM1 HG006504 / HG / NHGRI NIH HHS / United States
RC2 NS070477 / NS / NINDS NIH HHS / United States