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Abstract：
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.
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.
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.
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.
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.
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.
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.
摘要：
MONA,代表多心骨质溶解的光谱，皮下结节,和关节病,是一种由基质金属肽酶2（MMP2）基因突变引起的超罕见常染色体隐性遗传疾病。迄今为止只有44个人，已报道携带22种不同的突变。在这里，我们报道了两个具有相同纯合MMP2基因突变的兄弟，但是表型明显不同。
从受影响的兄弟和父母中分离基因组DNA。从较年轻的患者（索引病例）中进行了骨活检。使用明胶酶谱分析了年轻患者血清和滑液中基质金属肽酶2（MMP2）的水平。
DNA分析揭示了基因外显子8上的纯合c.118.8C>A颠倒。受影响的兄弟具有相同的纯合变体，并且父母对该变体是杂合的。该变体已被报道为一个个体上的复合杂合突变,导致硬皮病样皮肤增厚。骨组织形态计量学提示骨小梁重塑和更新增加。酶谱显示，血清中MMP2的水平完全无法测量，并且在滑液中仅发现了分子量与MMP2相似的少量明胶溶解蛋白带。
尽管基因型相同，但这两个兄弟的发病年龄和综合征的表型严重程度都不同。年轻患者的角膜混浊导致视力下降。第一次在这种疾病中，混浊通过角膜移植成功治疗。
从受影响的兄弟和父母中分离基因组DNA。从较年轻的患者（索引病例）中进行了骨活检。使用明胶酶谱分析了年轻患者血清和滑液中基质金属肽酶2（MMP2）的水平。
DNA分析揭示了基因外显子8上的纯合c.118.8C>A颠倒。受影响的兄弟具有相同的纯合变体，并且父母对该变体是杂合的。该变体已被报道为一个个体上的复合杂合突变,导致硬皮病样皮肤增厚。骨组织形态计量学提示骨小梁重塑和更新增加。酶谱显示，血清中MMP2的水平完全无法测量，并且在滑液中仅发现了分子量与MMP2相似的少量明胶溶解蛋白带。
尽管基因型相同，但这两个兄弟的发病年龄和综合征的表型严重程度都不同。年轻患者的角膜混浊导致视力下降。第一次在这种疾病中，混浊通过角膜移植成功治疗。
