Absence of MMP2 mutation in idiopathic multicentric osteolysis with nephropathy

The genetic basis of idiopathic multicentric osteolysis with nephropathy is unknown. This disorder is typically a sporadic, but sometimes an autosomal dominant, condition featuring carpal-tarsal destruction and nephropathy causing renal failure. Loss-of-function mutation within the gene encoding matrix metalloproteinase 2 (MMP2) causes the autosomal recessive disorder nodulosis-arthropathy-osteolysis syndrome characterized by carpal-tarsal destruction, subcutaneous nodules, and generalized osteoporosis. We questioned whether sporadic idiopathic multicentric osteolysis with nephropathy is allelic with nodulosis-arthropathy osteolysis syndrome and undertook sequence analysis of the matrix metalloproteinase 2 gene in three unrelated affected boys. Although symptoms appeared by age 2 years, idiopathic multicentric osteolysis was diagnosed at ages 5, 5, and 12 years with flares of pain and limited motion or swelling of wrists, ankles, elbows, knees, and shoulders. Proteinuria was present on referral at ages 8, 7, and 12 years, respectively. Kidney transplantation was necessary for one boy at age 17 years. Coding exons and adjacent mRNA splice sites of the matrix metalloproteinase 2 gene were analyzed by polymerase chain reaction amplification and DNA sequencing. Matrix metalloproteinase 2 gene analysis was negative for mutation in the three patients. Sequence analysis of the matrix metalloproteinase 2 gene shows sporadic idiopathic multicentric osteolysis with nephropathy is not allelic to nodulosis-arthropathy-osteolysis syndrome. The genetic bases of idiopathic multicentric osteolysis disorders remain unknown.