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.