J Korean Med Sci.  2009 Jun;24(3):433-437. 10.3346/jkms.2009.24.3.433.

ACVR1 Gene Mutation in Sporadic Korean Patients with Fibrodysplasia Ossificans Progressiva

• Lee DY
• Cho TJ
• Lee HR
• Park MS
• Yoo WJ
• Chung CY
• Choi IH

• KMID: 1779159
• DOI: http://doi.org/10.3346/jkms.2009.24.3.433

Abstract

Fibrodysplasia ossificans progressiva (FOP; OMIM 135100) is a rare but extremely disabling genetic disorder of the skeletal system, and is characterized by the progressive development of ectopic ossification of skeletal muscles and subsequent joint ankylosis. The c.617G>A; p.R206H point mutation in the activin A type I receptor (ACVR1) gene has been reported to be a causative mutation of FOP. In the present study, mutation analysis of the ACVR1 gene was performed in 12 patients diagnosed or suspected to have FOP. All patients tested had a de novo heterozygous point mutation of c.617G>A; p.R206H in ACVR1. Mutation analysis confirmed a diagnosis of FOP in patients with ambiguous features, and thus, could be used for diagnostic purposes. Early confirmation through mutation analysis would allow medical professionals to advise on the avoidance of provoking events to delay catastrophic flare-ups of ectopic ossifications.

Keyword

Myositis Ossificans; Mutation Analysis; ACVR1 Gene

MeSH Terms

Activin Receptors, Type I/*genetics
Adolescent
Adult
Asian Continental Ancestry Group/*genetics
Base Sequence
Child
Female
Genetic Predisposition to Disease
Heterozygote
Humans
Korea
Male
Myositis Ossificans/*diagnosis/genetics/radiography
Point Mutation
Young Adult

Figure

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  Fig. 1 Radiographic findings of FOP patients with unambiguous clinical features. Infiltration of paraspinal muscles mimicking a tumorous condition (A), ossification around the neck (B), thoracolumbar spine (C), and left thigh, which caused permanent loss of motion (D).

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  Fig. 2 Radiographic findings suggestive of FOP in a patient with ambiguous clinical features (case 2). (A) This patient showed no ectopic ossification but an osteochondroma-like bony spurs were observed on both distal femora, (B) Big toe abnormalities in this patient showed a slanting of metatarso-phalangeal joint (hallux valgus deformity).

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  Fig. 3 Mutation analysis of the ACVR1 in FOP patients with definite clinical manifestations. (A) Direct sequencing of the PCR products of the ACVR1 showed the presence of the c.617G>A mutation. R=adenine or guanine, (B) Restriction endonuclease digestion of the PCR product (350 bp). The G allele (control) was digested by Cac8I to produce three bands, whereas the A allele appeared as two bands. Because FOP patients were heterozygous for this mutation, the 139 bp and 114 bp bands were also presented. The PCR product not digested with HphI corresponds to the G allele (control) in contrast to digested products corresponding to the A allele (FOP).

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