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[A Chinese girl with fibrodysplasia ossificans progressiva caused by a de novo mutation R206H in ACVR1 gene].
Zhonghua Er Ke Za Zhi. 2008 Mar; 46(3):215-9.ZE

Abstract

OBJECTIVE

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant inherited disease caused by mutations of ACVR1 gene and can be inherited from either mother or father. FOP is characterized by the presence of malformations of the big toes and of progressive extra-skeletal ossification. Direct sequence analyses of genomic DNA have demonstrated that there is an identical single nucleotide substitution (c617G-->A, R206H) in the glycine-serine (GS) activation domain of ACVR1 gene, responsible for all affected individuals reported so far. We report a Chinese girl with typical FOP characteristics, in whom the same mutation in ACVR1 was identified.

METHODS

Clinical diagnosis was based on physical examination, radiological findings, and biochemical tests. For mutation detection, peripheral blood was obtained with informed consent from the patient and the parents. Genomic DNA was extracted from peripheral blood using standard method. Exon 4 of ACVR1 was amplified by polymerase chain reaction (PCR), and the PCR products were subjected to automatic DNA sequencing.

RESULTS

The affected girl is 3-year-old and showed typical clinical manifestations of FOP. She had malformations of the halluces at birth and subsequently progressive extra-skeletal ossification developed at the age of 8 - 9 months. Then, she gradually developed stiffness of the knee joint and neck but remained ambulant. Radiographic changes were observable, e.g., the extra-skeletal ossification was found at cervical spine. Her mother has congenital malformations of the halluces, but had no postnatal progressive extra-skeletal ossification. Her father and other family members are normal. With direct sequencing of the PCR products, a G to A substitution at c617 of ACVR1 (R206H) was detected in the patient only but not in her parents. Paternity analysis suggested that it is a de novo mutation.

CONCLUSION

This is the first case reported in a Chinese patient with FOP in the mainland of China, which was confirmed by direct sequencing. Although sporadic cases of FOP have been reported in diverse geographic and ethnic group, the mutations of ACVR1 c617 (R206H) are identical up to now. The presence of mutation hot spot facilitates molecular diagnosis in clinical practice. Genetic detection is important for FOP patients to avoid misdiagnosis and further damages, including those from medical intervention.

Authors+Show Affiliations

Department of Medical Genetics, Chinese Academy of Medical Sciences, Beijing 100005, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
English Abstract
Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

19099712

Citation

Zhou, Qing, et al. "[A Chinese Girl With Fibrodysplasia Ossificans Progressiva Caused By a De Novo Mutation R206H in ACVR1 Gene]." Zhonghua Er Ke Za Zhi = Chinese Journal of Pediatrics, vol. 46, no. 3, 2008, pp. 215-9.
Zhou Q, Meng Y, Su L, et al. [A Chinese girl with fibrodysplasia ossificans progressiva caused by a de novo mutation R206H in ACVR1 gene]. Zhonghua Er Ke Za Zhi. 2008;46(3):215-9.
Zhou, Q., Meng, Y., Su, L., Zhao, S. M., Shi, H. P., & Huang, S. Z. (2008). [A Chinese girl with fibrodysplasia ossificans progressiva caused by a de novo mutation R206H in ACVR1 gene]. Zhonghua Er Ke Za Zhi = Chinese Journal of Pediatrics, 46(3), 215-9.
Zhou Q, et al. [A Chinese Girl With Fibrodysplasia Ossificans Progressiva Caused By a De Novo Mutation R206H in ACVR1 Gene]. Zhonghua Er Ke Za Zhi. 2008;46(3):215-9. PubMed PMID: 19099712.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [A Chinese girl with fibrodysplasia ossificans progressiva caused by a de novo mutation R206H in ACVR1 gene]. AU - Zhou,Qing, AU - Meng,Yan, AU - Su,Liang, AU - Zhao,Shi-min, AU - Shi,Hui-ping, AU - Huang,Shang-zhi, PY - 2008/12/23/entrez PY - 2008/12/23/pubmed PY - 2010/12/14/medline SP - 215 EP - 9 JF - Zhonghua er ke za zhi = Chinese journal of pediatrics JO - Zhonghua Er Ke Za Zhi VL - 46 IS - 3 N2 - OBJECTIVE: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant inherited disease caused by mutations of ACVR1 gene and can be inherited from either mother or father. FOP is characterized by the presence of malformations of the big toes and of progressive extra-skeletal ossification. Direct sequence analyses of genomic DNA have demonstrated that there is an identical single nucleotide substitution (c617G-->A, R206H) in the glycine-serine (GS) activation domain of ACVR1 gene, responsible for all affected individuals reported so far. We report a Chinese girl with typical FOP characteristics, in whom the same mutation in ACVR1 was identified. METHODS: Clinical diagnosis was based on physical examination, radiological findings, and biochemical tests. For mutation detection, peripheral blood was obtained with informed consent from the patient and the parents. Genomic DNA was extracted from peripheral blood using standard method. Exon 4 of ACVR1 was amplified by polymerase chain reaction (PCR), and the PCR products were subjected to automatic DNA sequencing. RESULTS: The affected girl is 3-year-old and showed typical clinical manifestations of FOP. She had malformations of the halluces at birth and subsequently progressive extra-skeletal ossification developed at the age of 8 - 9 months. Then, she gradually developed stiffness of the knee joint and neck but remained ambulant. Radiographic changes were observable, e.g., the extra-skeletal ossification was found at cervical spine. Her mother has congenital malformations of the halluces, but had no postnatal progressive extra-skeletal ossification. Her father and other family members are normal. With direct sequencing of the PCR products, a G to A substitution at c617 of ACVR1 (R206H) was detected in the patient only but not in her parents. Paternity analysis suggested that it is a de novo mutation. CONCLUSION: This is the first case reported in a Chinese patient with FOP in the mainland of China, which was confirmed by direct sequencing. Although sporadic cases of FOP have been reported in diverse geographic and ethnic group, the mutations of ACVR1 c617 (R206H) are identical up to now. The presence of mutation hot spot facilitates molecular diagnosis in clinical practice. Genetic detection is important for FOP patients to avoid misdiagnosis and further damages, including those from medical intervention. SN - 0578-1310 UR - https://www.unboundmedicine.com/medline/citation/19099712/[A_Chinese_girl_with_fibrodysplasia_ossificans_progressiva_caused_by_a_de_novo_mutation_R206H_in_ACVR1_gene]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&issn=0578-1310&year=2008&vol=46&issue=3&fpage=215 DB - PRIME DP - Unbound Medicine ER -