A novel mutation in the matrix metallopeptidase 2 coding gene associated with intrafamilial variability of multicentric osteolysis, nodulosis, and arthropathy

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Kroger , L , Löppönen , T , Ala-Kokko , L , Kröger , H , Jauhonen , H-M , Lehti , K & Jaaskelainen , J 2019 , ' A novel mutation in the matrix metallopeptidase 2 coding gene associated with intrafamilial variability of multicentric osteolysis, nodulosis, and arthropathy ' , Molecular Genetics & Genomic Medicine , vol. 7 , no. 8 , 802 . https://doi.org/10.1002/mgg3.802

Title: A novel mutation in the matrix metallopeptidase 2 coding gene associated with intrafamilial variability of multicentric osteolysis, nodulosis, and arthropathy
Author: Kroger, Liisa; Löppönen, Tuija; Ala-Kokko, Leena; Kröger, Heikki; Jauhonen, Hanna-Mari; Lehti, Kaisa; Jaaskelainen, Jarmo
Contributor: University of Helsinki, INDIVIDRUG - Individualized Drug Therapy
Date: 2019-08
Language: eng
Number of pages: 6
Belongs to series: Molecular Genetics & Genomic Medicine
ISSN: 2324-9269
URI: http://hdl.handle.net/10138/306375
Abstract: Background MONA, which stands for a spectrum of Multicentric Osteolysis, subcutaneous Nodulosis, and Athropathia, is an ultra rare autosomal recessive disorder caused by mutations in the matrix metallopeptidase 2 (MMP2) gene. To date only 44 individuals, carrying 22 different mutations have been reported. Here we report on two brothers with identical homozygous MMP2 gene mutations, but with clearly different phenotypes. Methods Genomic DNA was isolated from the affected brothers and the parents. An iliac crest bone biopsy was taken from the younger patient (index case). The level of matrix metallopeptidase 2 enzyme (MMP2) in serum and synovial fluid of the younger patient was analyzed using gelatin zymography. Results The DNA analysis revealed a homozygous c.1188C>A transversion on exon 8 of the gene. The affected brothers had the same homozygous variant and the parents were heterozygous to this variant. This variant has been reported as a compound heterozygous mutation on one individual resulting in scleroderma like skin thickening. Bone histomorphometry indicated increased trabecular bone remodeling and turnover. The zymography revealed that the level of MMP2 was completely nonmeasurable in the serum and only a minor gelatinolytic protein band of about similar molecular weight as MMP2 was found in the synovial fluid. Conclusions Both the age at the onset and the phenotypic severity of the syndrome in these two brothers were different despite identical genotypes. The younger patients had corneal opacities leading to deteriorating visual acuity. For the first time in this disease, opacities were successfully treated with corneal transplantations.
Subject: arthropathy
joint contractures
matrix metallopeptidases
MONA
Osteolysis
MMP2
ARTHRITIS
CHILDREN
DOMAIN
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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