Cardiopulmonary function in fibrodysplasia ossificans progressiva.

Connor, J. M.; Evans, Cyril; Da, Evans

doi:10.1136/thx.36.6.419

Cited by 33 publications

(22 citation statements)

References 17 publications

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“…Pneumonia, predisposed to by chest wall fixation, has been the usual terminal event, both in published reports and in the present series. 20 There is no evidence, either from published reports or the present investigation, that the FOP gene is ever non-penetrant. For if this were the case, and the patient had normal fertility, then instances of affected sibs with normal parents would have been expected.…”

Section: Discussioncontrasting

confidence: 63%

Genetic aspects of fibrodysplasia ossificans progressiva.

Connor¹,

Da²

1982

Journal of Medical Genetics

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113

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Section: Discussioncontrasting

confidence: 63%

Genetic aspects of fibrodysplasia ossificans progressiva.

Connor¹,

Da²

1982

Journal of Medical Genetics

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113

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“…Although disease progression is variable (4,10,11), heterotopic ossification typically leads to extra-articular ankylosis of the major joints of the axial and appendicular skeleton, rendering movement impossible (4,(12)(13)(14)(15). Death often results from severe restrictive disease of the chest wall (1,16,17). At present, there is no effective prevention or treatment (18)(19)(20).…”

mentioning

confidence: 99%

Linkage exclusion and mutational analysis of the noggin gene in patients with fibrodysplasia ossificans progressiva (FOP)

Xu¹,

Feldman²,

Merrer

et al. 2000

Clinical Genetics

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Fibrodysplasia ossificans progressiva (FOP) is an extremely rare and disabling genetic disorder characterized by congenital malformation of the great toes and by progressive heterotopic endochondral ossification in predictable anatomical patterns. Although elevated levels of bone morphogenetic protein 4 (BMP4) occur in lymphoblastoid cells and in lesional cells of patients with FOP, mutations have not been identified in the BMP4 gene, suggesting that the mutation in FOP may reside in a BMP4-interacting factor or in another component of the BMP4 pathway. A powerful antagonist of BMP4 is the secreted polypeptide noggin. A recent case report described a heterozygous 42-bp deletion in the protein-coding region of the noggin gene in a patient with FOP. In order to determine if noggin mutations are a widespread finding in FOP, we examined 31 families with 1 or more FOP patients. Linkage analysis with an array of highly polymorphic microsatellite markers closely linked to the noggin gene was performed in four classically-affected multigenerational FOP families and excluded linkage of the noggin locus to FOP (the multipoint lod score was -2 or less throughout the entire range of markers). We sequenced the noggin gene in affected members of all four families, as well as in 18 patients with sporadic FOP, and failed to detect any mutations. Single-strand conformation polymorphism (SSCP) analysis of 4 of these patients plus an additional 9 patients also failed to reveal any mutations. Among the samples analyzed by SSCP and DNA sequencing was an independently obtained DNA sample from the identical FOP patient previously described with the 42-bp noggin deletion; no mutation was detected. Examination of the DNA sequences of 20 cloned noggin PCR products, undertaken to evaluate the possibility of a somatic mutation in the noggin gene which could be carried by a small subset of white blood cells, also failed to detect the presence of the reported 42-bp deletion. We conclude that mutations in the coding region of noggin are not associated with FOP.

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“…Restrictive lung disease is prevalent due to chest wall ossification, and may lead to pulmonary hypertension [7]. Pulmonary complications reduce survival of patients with FOP [4,8,9]. Spinal deformities [10], dependence on diaphragmatic breathing, and increased risk of pulmonary infections [11] also reduce the life span of patients with FOP.…”

Section: Discussionmentioning

confidence: 98%