Genetics of arthrogryposis: Linkage analysis approach

Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of congenital contracture syndromes, some of which are hereditary. To date, four genetic loci associated with autosomal recessive arthrogryposis syndromes have been identified using the powerful tools of genome-wide linkage analysis and homozygosity mapping. In the consanguineous inbred Bedouin population in southern Israel there is an unusually high incidence of hereditary arthrogryposis. We hypothesized the high incidence of this phenotype in this specific cohort might be due to a founder effect: a mutation that occurred several generations ago, spread throughout various tribes in that population in recent generations and causes the phenotype in its homozygous form. Using linkage analysis studies, we showed the hereditary arthrogryposis in those tribes does not stem from a single genetic defect. Thus, there is genetic heterogeneity of congenital arthrogryposis in this population: the same phenotype is caused by mutations in different genes, yet to be unraveled. Level of Evidence: Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.