Sinet P M, Théophile D, Rahmani Z, Chettouh Z, Blouin J L, Prieur M, Noel B, Delabar J M
URA CNRS 1335, Laboratoire de Biochimie Génétique, Hôpital Necker, Paris, France.
Biomed Pharmacother. 1994;48(5-6):247-52. doi: 10.1016/0753-3322(94)90140-6.
Phenotypic and molecular analysis of individuals with partial trisomy 21 can be used to determine which regions of chromosome 21 are involved in the pathogenesis of specific features of Down's Syndrome. Using dosage analysis of 27 sequences we defined, at the molecular level, the extent of the chromosome 21 duplication in ten individuals with partial trisomy 21. Phenotype-genotype correlations led to the definition of minimal regions, the duplications of which are linked to the expression of 23 clinical features of Down's Syndrome. The D21S55 region or Down's Syndrome Chromosome Region 1 (DCR1) (1/20 of the long arm), on 21q22.2-21q22.3 proximal, is involved in four cardinal features of the disease: mental retardation, growth retardation, muscular hypotonia and joint hyperlaxity, and in eight of the 18 more common morphological anomalies of the face, hands and feet. Overlapping the DCR1, the D21S55-MX1 region or DCR2 (1/10 of the long arm), spanning 21q21.2 down to the 1/4th proximal part of 21q22.3, is involved in the features defined by the DCR1 plus congenital heart defect and five additional morphological anomalies. Thus, our results indicate that duplication of a relatively small region of chromosome 21 plays a critical role in the pathogenesis of the Down's phenotype.
对21号染色体部分三体个体进行表型和分子分析，可用于确定21号染色体的哪些区域与唐氏综合征特定特征的发病机制有关。通过对我们定义的27个序列进行剂量分析，我们在分子水平上确定了10例21号染色体部分三体个体中21号染色体重复的范围。表型-基因型相关性导致了最小区域的定义，这些区域的重复与唐氏综合征23种临床特征的表达相关。位于21q22.2-21q22.3近端的D21S55区域或唐氏综合征染色体区域1（DCR1）（长臂的1/20），与该疾病的四个主要特征有关：智力发育迟缓、生长发育迟缓、肌张力低下和关节过度松弛，以及面部、手部和足部18种较常见形态异常中的8种。与DCR1重叠的D21S55-MX1区域或DCR2（长臂的1/10），跨度从21q21.2到21q22.3近端的1/4处，与DCR1所定义的特征以及先天性心脏病和另外五种形态异常有关。因此，我们的结果表明，21号染色体相对较小区域的重复在唐氏综合征表型的发病机制中起关键作用。
