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A Recurrent Mutation c.617G>A in the ACVR1 Gene Causes Fibrodysplasia Ossificans Progressiva in Two Chinese Patients

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Abstract

Fibrodysplasia ossificans progressiva (FOP; OMIM 135100) is a rare heritable disorder of connective tissue characterized by congenital malformations of the great toes and recurrent episodes of painful soft tissue swelling that lead to heterotopic ossifications. Recent studies have shown that the ACVR1 (activin A receptor, type I; OMIM 102576) gene, which encodes the BMP type I receptor protein, is responsible for this disease. We observed two Chinese patients who suffered from progressive pain and ankylosis of major joints with congenital bilateral hallus valgus malformation, neck stiffness, and several posttraumatic ossified lesions on the head and dorsum. Both patients were diagnosed as having FOP. This study aimed to investigate the ACVR1 gene mutation in Chinese FOP patients. Direct sequence analysis of genomic DNA and restriction enzyme digestion demonstrated the presence of a single heterozygous c.617G>A (p.R206H) mutation in the ACVR1 gene in both patients. This mutation is first reported in Chinese patients with FOP and it was de novo in both affected families.

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Acknowledgments

The authors thank Dr. Huiyuan Luo (Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College), who provided helpful discussion. The research funding was provided by the National Natural Science Foundation of China (NSFC) under Grant No. 30370781 and the Doctoral Fund of the Ministry of Education of China under Grant No. 20040023055.

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Authors and Affiliations

  1. Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Wangfujing, Dongcheng District, Beijing, 100730, China

    Yue Sun, Weibo Xia, Yan Jiang, Xiaoping Xing, Mei Li, Ou Wang, Huabing Zhang, Yingying Hu, Huaicheng Liu, Xunwu Meng & Xueying Zhou

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  1. Yue Sun
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  2. Weibo Xia
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  3. Yan Jiang
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  5. Mei Li
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  6. Ou Wang
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  7. Huabing Zhang
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  8. Yingying Hu
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  9. Huaicheng Liu
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  10. Xunwu Meng
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  11. Xueying Zhou
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Correspondence to Weibo Xia.

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Sun, Y., Xia, W., Jiang, Y. et al. A Recurrent Mutation c.617G>A in the ACVR1 Gene Causes Fibrodysplasia Ossificans Progressiva in Two Chinese Patients. Calcif Tissue Int 84, 361–365 (2009). https://doi.org/10.1007/s00223-009-9235-9

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  • DOI: https://doi.org/10.1007/s00223-009-9235-9

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