Reardon W
Mothercare Unit of Clinical Genetics and Fetal Medicine, London, U.K.
Prenat Diagn. 1996 Dec;16(13):1221-36. doi: 10.1002/(SICI)1097-0223(199612)16:13<1221::AID-PD97>3.0.CO;2-E.
The emerging data of the last few years outlining the molecular basis of skeletal dysplasias has been instructive in several respects. The number of genetic loci involved appears to be much fewer than anticipated. This is offset by the identification of several instances where phenotypically distinct entities are found to be allelic variants. With respect to diagnosis by DNA, most of the conditions recognized have several different mutations described. Consequently, while mutation analysis may be possible in a given case, close liaison with the investigating laboratory is essential if optimal results are to be obtained. Achondroplasia is unusual in that there is a common mutation and the other mutations related to the phenotype appear to cluster to a few codons. This review highlights the relationship between phenotypes of skeletal malformation, their underlying loci and mutations. These mutations appear to mediate their phenotypic effects through a diverse range of genetic mechanisms.
过去几年中涌现出的关于骨骼发育异常分子基础的数据在几个方面都具有启发性。涉及的基因座数量似乎比预期的要少得多。这一点因发现了几个表型不同的实体是等位基因变体的实例而得到弥补。关于通过DNA进行诊断，大多数已确认的病症都描述了几种不同的突变。因此，虽然在特定病例中进行突变分析可能可行，但要获得最佳结果，与研究实验室密切联系至关重要。软骨发育不全不同寻常之处在于存在一个常见突变，而与该表型相关的其他突变似乎集中在少数几个密码子上。本综述强调了骨骼畸形表型、其潜在基因座和突变之间的关系。这些突变似乎通过多种遗传机制介导其表型效应。
