Abstract
Fibrodysplasia ossificans progressiva (FOP) is a severely disabling, autosomal-dominant disorder of connective tissue and is characterized by postnatal progressive heterotopic ossification of muscle, tendon, ligament, and fascia and by congenital malformation of the great toes. To identify the chromosomal location of the FOP gene, we conducted a genomewide linkage analysis, using four affected families with a total of 14 informative meioses. Male-to-male transmission of the FOP phenotype excluded X-linked inheritance. Highly polymorphic microsatellite markers covering all human autosomes were amplified by use of PCR. The FOP phenotype is linked to markers located in the 4q27-31 region (LOD score 3.10 at recombination fraction 0). Crossover events localize the putative FOP gene within a 36-cM interval bordered proximally by D4S1625 and distally by D4S2417. This interval contains at least one gene involved in the bone morphogenetic protein-signaling pathway.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 128-135 |
| Number of pages | 8 |
| Journal | American journal of human genetics |
| Volume | 66 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2000 |
Funding
The authors gratefully acknowledge valuable scientific discussions with our colleagues Drs. Gregory Hahn, Victor McKusick, Richard Spielman, Jeffrey Tabas, and Michael Zasloff and the valuable technical contributions of Heather Mitchell and Mei-qi Xu. This work was supported in part by grants from the International Fibrodysplasia Ossificans Progressiva Association, the Ian Cali Fund for FOP Research, the Isaac and Rose Nassau Professorship of Orthopaedic Molecular Medicine, the National Institutes of Health (grant 2R01-AR41916-04), the European Neuromuscular Center, the Association Française Contre Les Myopathies, and the Medical Research Council of Great Britain.
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)