DELETION OF 19 BASE-PAIRS IN INTRON-13 OF THE GENE FOR THE PRO-ALPHA-2(I) CHAIN OF TYPE-I PROCOLLAGEN (COL1A2) CAUSES EXON SKIPPING IN A PROBAND WITH TYPE-I OSTEOGENESIS IMPERFECTA

作者：ZHUANG JP; TROMP G; KUIVANIEMI H; NAKAYASU K; PROCKOP DJ

来源：Human Genetics, 1993, 91(3): 210-216.

Skin fibroblasts from a proband with mild osteogenesis imperfecta (type I) synthesized normal proalpha2(I) chains and shortened proalpha2(I) chains of type-I procollagen. The type-I collagen that contained the shortened alpha2(I) chains was thermally unstable in that it was cleaved at 30-degrees-C by a mixture of trypsin and chymotrypsin. The mutation generating the shortened proalpha2(I) chains was shown to be a deletion of 19 base pairs from +4 to +22 of intron 13 of the COL1A2 gene by sequencing of genomic DNA and allele-specific oligonucleotide hybridization. The same mutation was found in the proband's affected father. Probeprotection experiments with S1 nuclease demonstrated that about 88% of the RNA transcripts from the mutated allele were spliced by exon skipping from exon 12 to exon 14 and that about 12% of the RNA transcripts were normally spliced. There was no evidence for use of cryptic splice sites, even though two cryptic splice sites had more favorable statistical scores and DELTAG-degrees-37 values than the new site that was created by the mutation and that was used for splicing of 12% of the transcripts into a normal mRNA. Comparison of the results with observations on 17 previously reported mutations that produced in-frame deletions of amino acids from the triple-helical domain of type-I collagen indicated that deletions in the N-terminal half of the alpha2(I) chain tended to produce milder phenotypes than similar deletions elsewhere in the alpha1(I) or alpha2(I) chains.

• 出版日期1993-4