Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen.
Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen.
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DOI：
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发表时间：
1988-02
影响因子：
9.8
通讯作者：
P. Byers;P. Tsipouras;J. Bonadio;B. Starman;R. C. Schwartz
中科院分区：
文献类型：
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作者：
P. Byers;P. Tsipouras;J. Bonadio;B. Starman;R. C. Schwartz
为了解决不确定性的遗传围产期致死形式的成骨细胞（OI II型），我们收集了71个先证者的家庭数据和X光片，并分析了胶原蛋白的真皮成纤维细胞培养的43个先证者，19个父母对，和单亲的每一个额外的四个先证者。在65个家庭，其中有完整的数据，兄弟姐妹的大小，有复发的OI II型表型在5个家庭，使6（8.6%）的70个同胞受到影响。在两个复发的家庭，放射学表型是温和的，比其余的，其中一个家庭是近亲，建议常染色体隐性遗传。在其余的三个家庭没有证据的血缘关系，但在其中一个结构是兼容的性腺镶嵌在母亲。在对43名婴儿的细胞合成胶原蛋白的研究中，我们发现了两名先证者，他们的I型胶原蛋白基因之一的等位基因发生了单独的重排;但在其余的人中，有细微的突变破坏了I型胶原蛋白分子的正常三螺旋结构。在两个先证者中，我们发现了新生突变;在另外16个家族中，来自父母的细胞只产生正常的胶原蛋白，与后代的新突变相容。这些研究结果表明，OI II型表型是生物化学异质性，大多数结果从新的显性突变的基因编码I型胶原蛋白，和一些复发可以解释性腺镶嵌在父母之一。
To resolve uncertainty concerning the inheritance of the perinatal lethal form of osteogenesis imperfecta (OI type II), we collected family data and radiographs for 71 probands and analyzed the collagens synthesized by dermal fibroblastic cells cultured from 43 of the probands, 19 parental pairs, and single parents of each of four additional probands. In 65 families for which there were complete data on sibship size, there was recurrence of the OI type II phenotype in five families such that six (8.6%) of 70 sibs were affected. In two families with recurrence, the radiographic phenotype was milder than that for the remainder; and one of those families was consanguinous, suggesting autosomal recessive inheritance. In the remaining three families there was no evidence of consanguinity, but in one of them the structure was compatible with gonadal mosaicism in the mother. In studies of collagens synthesized by cells from 43 infants, we identified two probands with separate rearrangements in an allele of one of the genes of type I collagen; but in the rest there were subtle mutations that disrupted the normal triple-helix structure of type I collagen molecules. In two probands we identified de novo mutations; in 16 additional families cells from the parents made only normal collagens, compatible with new mutations in their offsprings. These findings indicate that the OI type II phenotype is biochemically heterogeneous, that the majority result from new dominant mutations in the genes encoding type I collagen, and that some recurrences can be accounted for by gonadal mosaicism in one of the parents.