Fine mapping places the gene for arthrogryposis multiplex congenita neuropathic type between D5S394 and D5S2069 on chromosome 5qter

Arthrogryposis multiplex congenita (AMC) is a heterogeneous symptom complex characterized by non-progressive joint contractures from birth that involv e more than one part of the body. In 1997, our group investigated a large I sraeli Arab inbred kindred that showed autosomal recessive inheritance of A MC neuropathic type, and we mapped the gene to 5qter between markers D5S145 6 and D5S498. Haplotype sharing studies revealed complete homozygosity in a ll affected individuals with marker D5S394, thus providing significant stat istical evidence in favor of linkage. In this study, we have undertaken fur ther fine mapping of this region of chromosome 5qter, and have examined sev eral additional markers. All the affected individuals showed complete homoz ygosity for the marker D5S394, and also for three additional markers that a re telomeric to marker D5S394 and situated 31766 bp, 58016 bp, and 58516 bp , respectively, from it. Analysis of the recombinant individuals has enable d us to narrow down the critical region to a distance of .442 Mb between ma rkers D5S394 and D5S2069. (C) 2001 Wiley-Liss, Inc.