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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 - J. Korean Med. Sci. (2009)

Bottom Line: 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.All patients tested had a de novo heterozygous point mutation of c.617G>A; p.R206H in ACVR1.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul, Korea.

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.

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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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Figure 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).

Mentions: Twelve patients were included in this study. The phenotypes of the patients are summarized in Table 1. Ten patients had definite clinical manifestations of FOP, i.e., progressive ectopic ossification with resultant joint ankylosis (Fig. 1). Detailed clinical manifestations in some patients (case 7, 8, and 10) have been reported previously (11). Two patients (cases 1 & 2) showed ambiguous clinical features. An 8-yr old boy (case 1) was referred under a diagnosis of hereditary multiple exostosis. He did not have any restriction of joint motion except for limitation of terminal flexion in both elbow joints. No soft tissue mass or ectopic ossification was observed in this patient except for an osteochondroma-like bony spur on the right distal humerus. However, he was suspected to have FOP due to big toe anomalies. A 15-yr-old girl (case 2) visited complaining of in-toeing gait and calf pain after exercise. Although having mild flexion contractures on both hip and knee joints, she was athletically active. No ectopic ossification observed except for osteochondroma-like bony spurs on both distal femora (Fig. 2A). Big toe anomalies (Fig. 2B) and the 5th finger symphalangism lead us to suspect FOP. The parents recalled that a subcutaneous painless migrating scalp nodule had been detected when she was 6 months old, which spontaneously resolved in 2 weeks. Mutation analysis revealed heterozygous c.617G>A; p.R206H mutation in ACVR1, and she started to experience series of flare-up at age of 16 yr.


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 - J. Korean Med. Sci. (2009)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2698188&req=5

Figure 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).
Mentions: Twelve patients were included in this study. The phenotypes of the patients are summarized in Table 1. Ten patients had definite clinical manifestations of FOP, i.e., progressive ectopic ossification with resultant joint ankylosis (Fig. 1). Detailed clinical manifestations in some patients (case 7, 8, and 10) have been reported previously (11). Two patients (cases 1 & 2) showed ambiguous clinical features. An 8-yr old boy (case 1) was referred under a diagnosis of hereditary multiple exostosis. He did not have any restriction of joint motion except for limitation of terminal flexion in both elbow joints. No soft tissue mass or ectopic ossification was observed in this patient except for an osteochondroma-like bony spur on the right distal humerus. However, he was suspected to have FOP due to big toe anomalies. A 15-yr-old girl (case 2) visited complaining of in-toeing gait and calf pain after exercise. Although having mild flexion contractures on both hip and knee joints, she was athletically active. No ectopic ossification observed except for osteochondroma-like bony spurs on both distal femora (Fig. 2A). Big toe anomalies (Fig. 2B) and the 5th finger symphalangism lead us to suspect FOP. The parents recalled that a subcutaneous painless migrating scalp nodule had been detected when she was 6 months old, which spontaneously resolved in 2 weeks. Mutation analysis revealed heterozygous c.617G>A; p.R206H mutation in ACVR1, and she started to experience series of flare-up at age of 16 yr.

Bottom Line: 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.All patients tested had a de novo heterozygous point mutation of c.617G>A; p.R206H in ACVR1.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul, Korea.

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.

Show MeSH
Related in: MedlinePlus