In two sisters with MONA born to consanguineous parents of Algerian origin and originally reported with Winchester syndrome by Lambert et al. (1989), Rouzier et al. (2006) identified a homozygous 3-bp deletion (1488delTGG) in exon 8 of the MMP2 gene, resulting in a loss of val400 in a highly conserved region in the third alpha-helix of the catalytic domain of the protein.

Martignetti et al. (2001) carried out a linkage analysis study on four consanguineous Saudi families affected with multicentric osteolysis, nodulosis, and arthropathy (MONA). There were 11 affected and 24 unaffected members of these families. Using homozygous-by-descent microsatellite markers followed by sequence analysis, the disease was localized to chromosome 16q12-21 and two homozygous family-specific mutations were identified in the MMP2 gene; in family 3 all affected patients had (TCA/TAA) homozygous nonsense mutation, resulting in p.Y244X substitution. This nonsense mutation caused deletion of the substrate-binding and catalytic site and the fibronectin type II-like and hemopexin/TIMP2 binding domains. A homozygous G/A missense mutation in exon 2 of the gene was found in all affected patients in family 1, resulting in p.R101H substitution. This missense mutation caused disruption of the hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion. No mutations were detected in the MPP2 gene in family 2, suggesting that undetected homozygous mutation in the promoter or intronic region could be the cause of the disease in the affected individuals. A homozygous polymorphism (G/T) was identified in exon 4 in affected patients, resulting in p.D210Y amino acid substitution. However, this polymorphism was found to be common among same unaffected and unrelated members of the Saudi tribe. Martignetti et al. (2001) indicated that this SNP could be useful in MMP2 gene association studies.