Single base mutation in the pro alpha 2(I) collagen gene that causes efficient splicing of RNA from exon 27 to exon 29 and synthesis of a shortened but in-frame pro alpha 2(I) chain.

Abstract

Single base mutation in the proa2(I) collagen gene that causes efficient splicing of RNA from exon 27 to exon 29 and synthesis of a shortened but in-frame proa2(I) chain (RNA splicing ABSTRACTPrevious observations demonstrated that a lethal variant of osteogenesis imperfecta had two altered alleles for proa2(I) chains of type I procollagen. One mutation produced a nonfunctioning allele in that there was synthesis of mRNA but no detectable synthesis of proa2(I) chains from the allele. The mutation in the other allele caused synthesis of

Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda.

“…Site directed mutagenesis of conserved sequences at the 5' intron splice site skipping rarely occurs with in vivo systems but is common with in vitro splicing systems (25). Naturally occurring splice site mutations that lead to exon skipping have rarely been reported (26). Mutations causing the skipping of exons 6 and 28 in the pro-a2(I) collagen chain mRNA have been reported (26,27).…”

“…Naturally occurring splice site mutations that lead to exon skipping have rarely been reported (26). Mutations causing the skipping of exons 6 and 28 in the pro-a2(I) collagen chain mRNA have been reported (26,27). Each of these mutations caused an in-frame exon deletion which resulted in short, inactive proteins.…”

“…Each of these mutations caused an in-frame exon deletion which resulted in short, inactive proteins. Tromp and Prockop (26) suggested that the preferred splicing pathway for a gene determines if an exon will be skipped or an intron will be left in the aberrant mRNA. In the case of the URO-D mutant described here, the preferred pathway would be to remove intron 6 before intron 5.…”

Molecular and genetic analyses of the Caenorhabditis elegans dpy-2 and dpy-10 collagen genes: a variety of molecular alterations affect organismal morphology.

“…The effects on splicing of mutations in the AG dinucleotide have been examined in a variety of systems (Aebi et al, 1986;Mitchell et al, 1986;Cladaras et al, 1987;Tromp and Prockop, 1988;Su and Lin, 1990;Carstens et al, 1991). In these studies, one or more of three effects is seen.…”

Osteogenesis imperfecta. The position of substitution for glycine by cysteine in the triple helical domain of the pro alpha 1(I) chains of type I collagen determines the clinical phenotype.

“…A variety of molecular defects have been found to cause OI, including gene rearrangements (3)(4)(5)(6), point mutations (7)(8)(9)(10), genomic deletions or splicing mutations that result in deletion of single exon sequences from the mature mRNA and thus the protein (1 1,12), mutations that alter the reading frame in the gene for either chain oftype I procollagen (I 3),2 and mutations 1. Abbreviations used in this paper: 01, osteogenesis imperfecta.…”