A novel glycine to glutamic acid substitution at position 343 in the α2 chain of type I collagen in an individual with lethal osteogenesis imperfecta

Thirty-three novel COL1A1 and COL1A2 mutations in patients with osteogenesis imperfecta types I-IV

“…In contrast, the mutations described in the present report were associated with non-lethal forms of OI. Mutations in codons 1 to 439 of COL1A2 have been associated with a non-lethal phenotype according to the 'regional model' of the OI genotype/phenotype relationship (Marini et al 1999): two of the Gly→Glu mutations discussed here (Gly343Glu, Rose et al 1993; Gly436Glu, present report) fall within close proximity of each other in this region, yet the phenotypes vary. Furthermore, four of the fourteen COL1A2 glycine substitutions in the present report are within the lethal region according to the model (Gly481Arg, Gly511Ser, Gly538Arg, Gly574Asp), yet they are associated with moderate phenotypes.…”

“…The substitution of glutamic acid for glycine is a rare event, with only one previous report in the literature (Rose et al 1993). In the report by Rose et al, a Gly343Glu mutation was found in COL1A2 which resulted in a 'lethal' (OI type II) phenotype.…”

Mutations in fibrillar collagens (types I, II, III, and XI), fibril-associated collagen (type IX), and network-forming collagen (type X) cause a spectrum of diseases of bone, cartilage, and blood vessels

“…These methods included S1 nuclease and RNase probe protection experiments, as well as chemical modification or cleavage of heteroduplexes (see Cotton et al, 1988;Cotton, 1993;Grompe, 1993;Shikata et al, 1995). Detection of mutations was facilitated by the advent of PCR (Saiki et al, 1985;Shikata et al, 1995), by the development of methods for the screening of PCR products for the presence of mutations by gel electrophoresis such as single-stranded conformational polymorphisms (SSCP), denaturing gradient gel electrophoresis (DGGE) and conformation-sensitive gel electrophoresis (CSGE), and by protocols for direct sequencing of PCR products (Bateman et al, 1993;Cotton, 1993;Earley et al, 1993Earley et al, , 1994Ganguly et al, 1993;Mackay et al, 1993;Rose et al, 1993;Sztrolovics et al, 1993;Tromp et al, 1993;Spotila et al, 1994). Analysis of the cDNA has the disadvantage that a biopsy from the tissue in which the particular collagen is expressed must be obtained, whereas an analysis that is based on genomic DNA can be carried out with DNA isolated from blood.…”

Direct sequencing of PCR products derived from cDNAs for the proα1 and proα2 chains of type I procollagen as a screening method to detect mutations in patients with osteogenesis imperfecta

“…In the first step, an attempt is made to define a region in either the COLlAl or COL2Al gene that may contain a mutation by procedures such as analysis of the type I procollagen synthesized by cultured skin fibroblasts including pepsin and trypsin digestions and cyanogen bromide peptide mapping (see Kuivaniemi et al, 1991;Byers, 1993), S1 nuclease and RNase probe protection with fibroblast mRNA, chemical modification, or cleavage of cDNA:genomic DNA or DNA:mRNA heteroduplexes (Bateman et al, 1993), and conformational polymorphisms (SSCP) of cDNAs amplified by PCR Rose et al, 1993). After the region containing the mutation is identified, the mutation itself is defined by sequencing cDNA or genomic DNA from the region.…”

“…Detection of mutations in cDNAs was facilitated by the advent of PCR (Saiki et al, 1985) and development of methods by which DNA or RNA:DNA fragments could be scanned for the presence of single base mutations (Cotton et al, 1988;Ganguly et al, 1989Ganguly et al, , 1993Zhuang et al, 1991;Bateman et al, 1993;Filie et al, 1993;Mackay et al, 1993;Rose et al, 1993;Sztrolovics et al, 1993). However, detection of mutations in type I procollagen has remained difficult for several reasons.…”