A 2ND LOCUS FOR MARFAN-SYNDROME MAPS TO CHROMOSOME-3P24.2-P25

Marfan syndrome (MFS) is an autosomal dominant connective-tissue disor der characterized by skeletal, ocular and cardiovascular defects of hi ghly variable expressivity. The diagnosis relies solely on clinical cr iteria requiring anomalies in at least two systems. By excluding the c hromosome 15 disease locus, fibrillin 1 (FBN1), in a large French fami ly with typical cardiovascular and skeletal anomalies, we raised the i ssue of genetic heterogeneity in MFS and the implication of a second l ocus (MFS2). Linkage analyses, performed in this family, have localize d MFS2 to a region of 9 centiMorgans between D3S1293 and D3S1283, at 3 p24.2-p25. In this region, the highest lod score was found with D3S233 6, of 4.89 (theta=0.05). By LINKMAP analyses, the most probable positi on for the second locus in MFS was at D3S2335.