Pruchno C J, Cohn D H, Wallis G A, Willing M C, Starman B J, Zhang X M, Byers P H
Department of Medicine, University of Washington, Seattle 98195.
Hum Genet. 1991 May;87(1):33-40. doi: 10.1007/BF01213088.
Most individuals with osteogenesis imperfecta (OI) are heterozygous for dominant mutations in one of the genes that encode the chains of type I collagen. Each of the more than 30 mutations characterized to date has been unique to the affected member(s) of the family. We have determined that two individuals with a progressive deforming variety of OI, OI type III, have the same new dominant mutation [alpha 1(I)gly154 to arg] and that two unrelated infants with perinatal lethal OI, OI type II, share a second new dominant mutation [alpha 1(I)gly1003 to ser]. These mutations occurred at CpG dinucleotides, in a manner consistent with deamination of a methylated cytosine residue, and raise the possibility that CpG dinucleotides are common sites of recurrent mutations in collagen genes. Further, these findings confirm that the OI type-III phenotype, previously thought to be inherited in an autosomal recessive manner, can result from new dominant mutations in the COL1A1 gene of type-I collagen.
大多数成骨不全症（OI）患者是编码I型胶原链的基因之一发生显性突变的杂合子。迄今为止已鉴定出的30多种突变中的每一种对于受影响的家庭成员来说都是独特的。我们已确定两名患有进行性变形型OI（III型OI）的个体具有相同的新显性突变[α1（I）甘氨酸154突变为精氨酸]，并且两名患有围产期致死性OI（II型OI）的无关婴儿共享第二个新显性突变[α1（I）甘氨酸1003突变为丝氨酸]。这些突变发生在CpG二核苷酸处，其方式与甲基化胞嘧啶残基的脱氨一致，并增加了CpG二核苷酸是胶原基因中反复突变的常见位点的可能性。此外，这些发现证实，先前认为以常染色体隐性方式遗传的III型OI表型可能由I型胶原的COL1A1基因中的新显性突变引起。
