Early-onset Paget's disease of bone in a Mexican family caused by a novel tandem duplication (77dup27) in TNFRSF11A that encodes RANK.

ABSTRACT: Four heterozygous in-frame tandem duplications of different lengths in TNFRSF11A, the gene that encodes receptor activator of nuclear factor κB (RANK), constitutively activate RANK and lead to high turnover skeletal disease. Each duplication elongates the signal peptide of RANK. The 18-base pair (bp) duplication at position 84 (84dup18) causes familial expansile osteolysis (FEO), the 15-bp duplication at position 84 (84dup15) causes expansile skeletal hyperphosphatasia (ESH), the 12-bp duplication at position 90 (90dup12) causes panostotic expansile bone disease (PEBD), and the 27-bp duplication causes early-onset Paget's disease of bone (PDB2). The severity of the associated skeletal disease seems inversely related to the duplication's length. Additional 15- and 18-bp duplications of TNFR

SUBMITTER: Iwamoto SJ 

PROVIDER: S-EPMC7179970 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature