Type V collagen is a constituent of type I collagen-rich fibrils in many 
connective tissues and is a regulator of fibril diameter. In tissues, type V 
collagen is a heterotrimer with the molecular structure: alpha 1(V)2 alpha 2(V) 
or alpha 1(V) alpha 2(V) alpha 3(V). We report that genomic polymorphisms at the 
pro alpha 1(V) gene (COL5A1) locus cosegregated with the gravis form of 
Ehlers-Danlos syndrome (EDS) (type I) in a three generation family. Affected 
family members, who had classical features including joint hyperextensibility, 
fragile skin, and widened, atrophic scars, were heterozygous for a 4 bp deletion 
at positions from +3 to +6 of intron 65, which resulted in removal of exon 65 
sequences from processed mRNAs. Since exon 65 encodes 78 residues of the 
carboxyl propeptide, the expected result of this mutation is reduced efficiency 
in incorporating mutant pro alpha 1(V) chains into type V collagen molecules and 
reduced type V collagen synthesis. These studies indicate that heterozygous 
mutations in COL5A1 can result in EDS type I. However, linkage studies in other 
EDS I families indicate the disorder is heterogeneous; linkage to both COL5A1 
and COL5A2 was excluded in two other families with EDS I while a fourth family 
was concordant for linkage to COL5A1 (Z = 2.11; theta = 0.00).