Precise localisation of 3p25 breakpoints in four patients with the 3p-syndrome
Precise localisation of 3p25 breakpoints in four patients with the 3p-syndrome
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DOI：
10.1136/jmg.33.10.842
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发表时间：
1996-10-01
影响因子：
4
通讯作者：
Smith, DI
中科院分区：
文献类型：
--
作者：
Drumheller, T;McGillivray, BC;Smith, DI
在3 p-综合征患者中，3 p25-pter的半合子缺失与严重的生长障碍、特征性面部特征和智力低下有关。我们对4例3 p-综合征患者和1例更复杂的46，XY，der（3）t（3;？）（p25.3;？）。EBV转化的淋巴母细胞，从每个病人最初的特点是使用荧光原位杂交（FISH）和多态性微卫星分析。从体细胞杂交系中的正常3号染色体分离来自每个患者的3 p-染色体，随后用来自3 p25的多态性和单态性PCR可扩增标记进行分析。分析清楚地表明，所有五个断点都是不同的。此外，我们已经确定了酵母人工染色体，跨越所有四个3 p-患者的3 p25断点。其中两名患者的von Hippel-Lindau（VHL）肿瘤抑制基因被删除，尽管他们都没有出现VHL疾病的证据。在D3 S1585和D3 S1263之间具有最多着丝粒断裂点的患者具有最严重的临床表型，包括在具有更多端粒断裂点的四名患者中没有观察到的内膜垫缺陷。这项研究应该为3 P25中参与正常人类生长和发育的关键区域提供有用的见解。
In patients with the 3p- syndrome, hemizygous deletion of 3p25-pter is associated with profound growth failure, characteristic facial features, and mental retardation. We performed a molecular genetic analysis of 3p25 breakpoints in four patients with the 3p- syndrome, and a fifth patient with a more complex abnormality, 46,XY,der(3)t(3;?) (p25.3;?). EBV transformed lymphoblasts from each of the patients were initially characterised using fluorescent in situ hybridisation (FISH) and polymorphic microsatellite analyses. The 3p- chromosome from each patient was isolated from the normal chromosome 3 in somatic cell hybrid lines and subsequently analysed with polymorphic and monomorphic PCR amplifiable markers from 3p25. The analysis clearly shows that all five breakpoints are distinct. Furthermore, we have identified yeast artificial chromosomes that cross the 3p25 breakpoints of all four 3p-patients. Two of the patients were deleted for the von Hippel-Lindau (VHL) tumour suppressor gene, although neither has yet developed evidence of VHL disease. The patient with the most centromeric breakpoint, between D3S1585 and D3S1263, had the most severe clinical phenotype including an endocardial cushion defect that was not observed in any of the four patients who had more telomeric breakpoints. This study should provide useful insights into critical regions within 3P25 that are involved in normal human growth and development.