A mutation in the pro alpha 2(I) gene (COL1A2) for type I procollagen in Ehlers-Danlos syndrome type VII: evidence suggesting that skipping of exon 6 in RNA splicing may be a common cause of the phenotype.
 Fibroblasts from a proband with Ehlers-Danlos syndrome type VII synthesized approximately equal amounts of normal and shortened pro alpha 2(I) chains of type I procollagen.
 Nuclease S1 probe protection experiments with mRNA demonstrated that the pro alpha 2(I) chains were shortened because of a deletion of most or all of the 54 nucleotides in exon 6, the exon that contains codons for the cleavage site for procollagen N-proteinase.
 Sequencing of genomic clones revealed a single-base mutation that converted the first nucleotide of intron 6 from G to A.
 Therefore, the mutation was a change, in the -GT-consensus splice site, that produced efficient exon skipping.
 Allele-specific oligonucleotide hybridizations demonstrated that the proband's mother, father, and brother did not have the mutation.
 Therefore, the mutation was a sporadic one.
 Analysis of potential 5' splice sites in the 5' end of intron 6 indicated that none had favorable values by the two commonly employed techniques for evaluating such sites.
 The proband is the fourth reported proband with Ehlers-Danlos syndrome VII with a single-base mutation that causes skipping of exon 6 in the splicing of RNA from either the COL1A1 gene or COL1A2 gene.
 No other mutations in the two type I procollagen genes have been found in the syndrome.
 Therefore, such mutations may be a common cause of the phenotype.
 The primers developed should be useful in screening for the same or similar mutations causing the disease.
