EHLERS-DANLOS-SYNDROME TYPE VIIA AND VIIB RESULT FROM SPLICE-JUNCTIONMUTATIONS OR GENOMIC DELETIONS THAT INVOLVE EXON-6 IN THE COL1A1 AND COL1A2 GENES OF TYPE-I COLLAGEN

Ehlers-Danlos syndrome (EDS) type VII results from defects in the conv ersion of type I procollagen to collagen as a consequence of mutations in the substrate that alter the protease cleavage site (EDS type VIIA and VIIB) or in the protease itself (EDS type VIIC), We identified se ven additional families in which EDS type VII is either dominantly inh erited (one family with EDS type VIIB) or due to new dominant mutation s (one family with EDS type VIIA and five families with EDS type VIIB) , In six families, the mutations alter the consensus splice junctions, and, in the seventh family, the exon is deleted entirely, The COL1A1 mutation produced the most severe phenotypic effects, whereas those in the COL1A2 gene, regardless of the location or effect, produced conge nital hip dislocation and other joint instability that was sometimes v ery marked, Fractures are seen in some people with EDS type VII, consi stent with alterations in mineral deposition on collagen fibrils in bo ny tissues, These new findings expand the array of mutations known to cause EDS type VII and provide insight into genotype/phenotype relatio nships in these genes. (C) 1997 Wiley-Liss, Inc.