The First Report of Multicentric Carpotarsal Osteolysis Syndrome Caused by MAFB Mutation in Asian.
The First Report of Multicentric Carpotarsal Osteolysis Syndrome Caused by MAFB Mutation in Asian.
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DOI：
10.1155/2018/6783957
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发表时间：
2018
影响因子：
0.8
通讯作者：
Khositseth S
中科院分区：
文献类型：
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作者：
Choochuen P;Rojneuangnit K;Khetkham T;Khositseth S
多中心腕跗骨溶解综合征（MCTO）是一种罕见的骨骼疾病，其特征是与进行性肾病相关的侵袭性骨溶解。早期临床表现可模仿多关节型幼年特发性关节炎。自2012年以来，在所有MCTO患者中都发现了MAFB突变。因此，可以根据基因确认进行早期诊断。我们报告一例患有 MCTO 的泰国女性青少年矿物质骨病的临床表现和分子遗传学研究。她患有终末期肾病、双侧腕关节和踝关节畸形以及轻微的面部畸形特征。我们在第197位核苷酸处发现了从C到G的杂合错义突变（NM_005461.4；c.197C>G），预测密码子66处的氨基酸从丝氨酸变为半胱氨酸（p.Ser66Cys），并且该突变在亲本中不存在，表明是从头突变。该报告证实了先前 MAFB 突变与 MCTO 之间的联系。她在服用常规剂量的钙和活性维生素 D 后出现不明原因的高钙血症，这支持了 MafB 在 RANKL 介导的破骨细胞分化的负调节中的重要作用。因此，我们鼓励照顾 MCTO 患者的医生密切监测血清钙水平并进行基因研究，作为管理和调查的一部分。
Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by aggressive osteolysis associated with progressive nephropathy. The early clinical presentation can mimic polyarticular juvenile idiopathic arthritis. Since 2012, MAFB mutations have been discovered in all MCTO patients. Therefore, the early diagnosis can be made based on genetic confirmation. We report the clinical manifestation of mineral bone disease and the molecular genetic study of a Thai female adolescent with MCTO. She presented with end-stage renal disease, bilateral wrist and ankle joint deformities, and subtle facial dysmorphic features. We identified a heterozygous missense MAFB mutation at nucleotide 197 from C to G (NM_005461.4; c.197C>G), predicting the change of amino acid at codon 66 from serine to cysteine (p.Ser66Cys), and the mutation was absent in the parents, indicating a de novo mutation. This report confirms the previous link between MAFB mutation and MCTO. Her unexplained hypercalcemia after a regular dose of calcium and active vitamin D supported an important role of MafB in the negative regulation of RANKL-mediated osteoclast differentiation. Therefore, we would encourage the physicians who take care of MCTO patients to closely monitor serum calcium level and perform a genetic study as a part of the management and investigation.