Exome Sequencing of Chinese Patients With Anticitrullinated Protein Antibody-Positive Rheumatoid Arthritis in Singapore.

Objective: More than 130 susceptibility loci for rheumatoid arthritis (RA) have been identified with genome-wide association studies. To investigate the genetic predisposition of Chinese patients to anticitrullinated protein antibody (ACPA)-positive RA, we carried out an exome sequencing study.

Methods: Patients were recruited from 3 major public hospitals in Singapore: Tan Tock Seng Hospital (TTSH), Singapore General Hospital, and the National University Hospital.

Osteoblast-specific deletion of Hrpt2/Cdc73 results in high bone mass and increased bone turnover.

Inactivating mutations that lead to loss of heterozygosity within the HRPT2/Cdc73 gene are directly linked to the development of primary hyperparathyroidism, parathyroid adenomas, and ossifying fibromas of the jaw (HPT-JT). The protein product of the Cdc73 gene, parafibromin, is a core member of the polymerase-associated factors (PAF) complex, which coordinates epigenetic modifiers and transcriptional machinery to control gene expression. We conditionally deleted Cdc73 within mesenchymal progenitors or within mature osteoblasts and osteocytes to determine the consequences of parafibromin loss within the mesenchymal lineage.