The clinical features of homozygous alpha 2(I) collagen deficient osteogenesis imperfecta.

Abstract

The detailed clinical features and progress of a child with homozygous 22(I) collagen deficiency are described. Clinically, the disease presents as severe progressive Sillence type IlI osteogenesis imperfecta. The main biochemical defect is the synthesis of an abnormal pro 22(I) chain which does not associate with pro a I(I) chains and therefore is not incorporated into triple helical trimers of type I procollagen which can be used to assemble collagen fibres.

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.

“…Relatively few mutations that produce these disorders have been identified. A 4-bp deletion near the 3' end of the coding region of the proa2(I) chain that altered the last 12 residues of the chain and prevented its assembly into type I procollagen molecules produced an OI type III phenotype in the homozygous state but had little phenotypic effect in the heterozygotes (13,30). Deletion of single exons encoding domains near the amino-terminal end of the triple helix of the proa2(I) chain (11) or near the center of the triple helix (31) have produced mild-to-moderate phenotypes, as has a substitution of arginine for glycine near the carboxyl-terminal end of the triple-helical domain of proa2(I) (32).…”

A new osteogenesis imperfecta with improvement over time maps to 11q

“…OI is usually an autosomal dominant disorder, resulting from inheritance of a mutant gene or from a de novo mutation. However, autosomal recessive cases of OI have been reported, with altered COL1A2 only [Nicholls et al, 1984;Piihlajaniemi et al, 1984;Spotila et al, 1992;De Paepe et al, 1997]. Moreover, 6% of sporadic OI cases are due to mosaicism in one parent.…”

Extension of Phenotype Associated with Structural Mutations in Type I Collagen: Siblings with Juvenile Osteoporosis Have an α2(I)Gly436 → Arg Substitution

“…(9) Unglycosylated procollagens were obtained by labeling fibroblasts in the presence of 0.53 mM ␣,␣Ј-dipyridyl for 4 h. (9) Cyanogen bromide peptides were prepared by CNBr digestion of gel slices containing ␣1(I) or ␣2(I) chains, followed by electrophoresis on a 10% polyacrylamide urea-SDS gel. (10) …”