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Summary: Identification of a missense mutation ofc.3064G>A, Glyl022Ser in exon 43 of COLI Al gene in a girl with osteogenesis imperfecta type III: Osteogenesis imperfecta (OI) types I - V have been inherited in an autosomal dominant pattern. 01 type I is associated with mutations in COLI A I mostly due to a null allele. 01 types II ~ IV are associated with mutations in COLIA! or COLÌA2 and mostly are due to glycine substitutions. It has been suggested that the effect of glycine substitutions is position spécifie, and the substitution of glycine by serine has much less lethal effect than the substitutions by valine, aspartic acid, glutamic acid, arginine and cysteine. We report identification of c.3064G>A, GGT>AGT, Glyl022Ser (Gly^-^Ser8*1 in triple helix) in exon 43 of the COLI Al gene in an 8-year-old girl with OI type HI. Our report provides evidence that at triple helix glycine residue 844 (p.Gly 1 022), a glycine substitution by serine can result in OI type III but not a lethal outcome.
Key-words: COLI A I Genotype-phenotype - Osteogenesis imperfecta type III - Type I collagen.
[INTRODUCTION
Osteogenesis imperfecta (01) is a genetic disorder characterized by increased bone fragility, decreased bone mass and other connective-tissue manifestations such as blue sclerae, hyperlaxity of ligaments and skin, dentinogenesis imperfecta (DI), and hearing loss (10, 11). The incidence of 01 varies between 1:20,000 and 1:60,000 births (2, 7).
OI type I ~ type V have been inherited in an autosomal dominant pattern, and 01 type VI ~ type XII have been inherited in an autosomal recessive pattern. OI type I is associated with mutations in COLI Al mostly due to a null allele caused by deletions, duplications, nonsense mutations and frameshift mutations that cause a premature stop codon. 01 type II ~ type IV are associated with mutations in COLI A I or COLIA2 and mostly are due to glycine substitutions although other mutations such as splicing defects, deletions or duplications have been described. 01 type VI ~ type XII can be caused by homozygous or compound heterozygous mutations in FKBP10, CRTAP, LEPRE1, PPIB, SERPINH2, SP7 and SERPINF1, respectively.
In the autosomal dominant 01 types I ~ IV, the severity increases in the order of type I < type...