Chen C P, Lin S P, Suo Y N, Chern S R, Su J W, Wang W
Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
Genet Couns. 2012;23(3):359-65.
Osteogenesis imperfecta (OI) types I-V have been inherited in an autosomal dominant pattern. OI type I is associated with mutations in COL1A1 mostly due to a null allele. OI types II-IV are associated with mutations in COL1A1 or COL1A2 and mostly are due to glycine substitutions. It has been suggested that the effect of glycine substitutions is position specific, 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, Gly1022Ser (Gly(844) --> Ser844 in triple helix) in exon 43 of the COL1A1 gene in an 8-year-old girl with OI type III. Our report provides evidence that at triple helix glycine residue 844 (p.Gly1022), a glycine substitution by serine can result in OI type III but not a lethal outcome.
Ⅰ-Ⅴ型成骨不全症（OI）以常染色体显性模式遗传。Ⅰ型OI主要与COL1A1基因突变有关，多因无效等位基因所致。Ⅱ-Ⅳ型OI与COL1A1或COL1A2基因突变有关，多因甘氨酸替代所致。有人提出，甘氨酸替代的影响具有位置特异性，且丝氨酸替代甘氨酸的致死效应远低于缬氨酸、天冬氨酸、谷氨酸、精氨酸和半胱氨酸替代所致的效应。我们报告了在一名8岁Ⅲ型OI女童的COL1A1基因第43外显子中鉴定出c.3064G>A、GGT>AGT、Gly1022Ser（三螺旋中Gly(844) --> Ser844）。我们的报告提供了证据，表明在三螺旋甘氨酸残基844（p.Gly1022）处，丝氨酸替代甘氨酸可导致Ⅲ型OI，但不会导致致死结果。
