Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Fibrodysplasia ossificans progressiva

Die Fibrodysplasia ossificans progressiva ist eine autosomal dominante Erkrankung, die durch aktivierende Mutationen des Aktivinrezeptors 1 hervorgerufen wird und durch extraskelettale vornehmlich endochondrale Ossifikationen gekennzeichnet ist. Die Patienten sind zunehmend durch Knochendeformationen und durch solche Verknöcherungen in ihrer Beweglichkeit eingeschränkt.

Epidemiologie

Die Prävalenz der Erkrankung wird mit 1:1-2.000.000 angegeben. Die meisten Fälle sind Neumutationen, da aufgrund der massiven Skelettveränderungen die Reproduktionskapazität erheblich eingeschränkt ist.[1]

Symptome

Extraossäre Ossification
Bei der Fibrodysplasia ossificans progressiva befinden sich die Ossifikationen vornehmlich in Sehnen, Bändern, Skelettmuskeln und Faszien. Vor dem Erscheinen des Knochengewebes zeigen sich schmerzhafte inflammatorische Knoten (“flare-ups”).

Gliederung

Erbliche Erkrankungen mit heterotroper Knochenbildung
Fibrodysplasia ossificans progressiva
ACVR1
Hyperphosphatämische familiäre Tumorcalcinose
Progressive knöcherne Heteroplasie

Referenzen:

1.

Shore EM et al. (2006) A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva.

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2.

Lin GT et al. (2006) De novo 617G-A nucleotide mutation in the ACVR1 gene in a Taiwanese patient with fibrodysplasia ossificans progressiva.

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3.

Nakajima M et al. (2007) The ACVR1 617G>A mutation is also recurrent in three Japanese patients with fibrodysplasia ossificans progressiva.

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4.

Furuya H et al. (2008) A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H).

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5.

Bocciardi R et al. (2009) Mutational analysis of the ACVR1 gene in Italian patients affected with fibrodysplasia ossificans progressiva: confirmations and advancements.

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6.

Kaplan FS et al. (2009) Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1.

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7.

Petrie KA et al. (2009) Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients.

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8.

Barnett CP et al. (2011) Late-onset variant fibrodysplasia ossificans progressiva leading to misdiagnosis of ankylosing spondylitis.

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9.

Smith R et al. (1976) Myositis ossificans progressiva. Clinical features of eight patients and their response to treatment.

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10.

Shafritz AB et al. (1996) Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva.

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11.

Kan L et al. (2004) Transgenic mice overexpressing BMP4 develop a fibrodysplasia ossificans progressiva (FOP)-like phenotype.

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12.

Feldman G et al. (2000) Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31.

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13.

Lucotte G et al. (1999) A de novo heterozygous deletion of 42 base-pairs in the noggin gene of a fibrodysplasia ossificans progressiva patient.

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14.

Xu MQ et al. (2000) Linkage exclusion and mutational analysis of the noggin gene in patients with fibrodysplasia ossificans progressiva (FOP).

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15.

Lucotte G et al. (2000) Localization of the gene for fibrodysplasia ossificans progressiva (FOP) to chromosome 17q21-22.

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16.

Rogers JG et al. (1979) Fibrodysplasia ossificans progressiva. A survey of forty-two cases.

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17.

Sémonin O et al. (2001) Identification of three novel mutations of the noggin gene in patients with fibrodysplasia ossificans progressiva.

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18.

Xu MQ et al. (2002) Reported noggin mutations are PCR errors.

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19.

Warman ML et al. (2002) Significant difference of opinion regarding the role of noggin in fibrodysplasia ossificans progressiva.

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20.

Maxwell WA et al. (1977) Histochemical and ultrastructural studies in fibrodysplasia ossificans progressiva (myositis ossificans progressiva).

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21.

Daltroff G et al. (1992) [Fibromatosis and fibrodysplasia ossificans progressiva. An avoidable diagnostic error].

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22.

de la Peña LS et al. (2005) Fibrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis, misregulates cell surface expression and trafficking of BMPRIA.

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23.

Fontaine K et al. (2005) A new mutation of the noggin gene in a French Fibrodysplasia ossificans progressiva (FOP) family.

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24.

Kitterman JA et al. (2005) Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva.

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25.

Lucotte G et al. (2007) Mutations of the noggin and of the activin A type I receptor genes in fibrodysplasia ossificans progressiva (FOP).

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26.

Seemann P et al. (2008) The tale of FOP, NOGGIN and myristoylation: no data, no proof!

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27.

Kaplan FS et al. (2008) Response to "Mutations of the NOGGIN and of the activin A type I receptor genes in fibrodysplasia ossificans progressiva (FOP)" by Lucotte et al.

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28.

Shimono K et al. (2011) Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-γ agonists.

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29.

Rogers JG et al. (1979) Paternal age effect in fibrodysplasia ossificans progressiva.

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30.

Tünte W et al. (1967) [On the genetics of myositis ossificans progressiva].

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31.

Connor JM et al. (1982) Genetic aspects of fibrodysplasia ossificans progressiva.

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32.

Schroeder HW et al. (1980) The hand and foot malformations in fibrodysplasia ossificans progressiva.

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33.

Kaplan FS et al. (1993) The histopathology of fibrodysplasia ossificans progressiva. An endochondral process.

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34.

Kaplan FS et al. (1993) Genetic transmission of fibrodysplasia ossificans progressiva. Report of a family.

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35.

Connor JM et al. (1993) A three generation family with fibrodysplasia ossificans progressiva.

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36.

Cohen RB et al. (1993) The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients.

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37.

Janoff HB et al. (1996) Fibrodysplasia ossificans progressiva in two half-sisters: evidence for maternal mosaicism.

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38.

Beratis NG et al. (1976) Alkaline phosphatase activity in cultured skin fibroblasts from fibrodysplasia ossificans progressiva.

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