Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling, autoso mal-dominant disorder of connective tissue and is characterized by postnata l progressive heterotopic ossification of muscle, tendon, ligament, and fas cia and by congenital malformation of the great toes. To identify the chrom osomal 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. H ighly 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 prox imally by D4S1625 and distally by D4S2417. This interval contains at least one gene involved in the bone morphogenetic protein-signaling pathway.