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首页> 外文期刊>American journal of medical genetics, Part A >Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome.
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Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome.

机译：青少年息肉病（JP）和JP-HHT综合征中SMAD4突变的重叠光谱。

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摘要

Juvenile polyposis (JP) and hereditary hemorrhagic telangiectasia (HHT) are clinically distinct diseases caused by mutations in SMAD4 and BMPR1A (for JP) and endoglin and ALK1 (for HHT). Recently, a combined syndrome of JP-HHT was described that is also caused by mutations in SMAD4. Although both JP and JP-HHT are caused by SMAD4 mutations, a possible genotype:phenotype correlation was noted as all of the SMAD4 mutations in the JP-HHT patients were clustered in the COOH-terminal MH2 domain of the protein. If valid, this correlation would provide a molecular explanation for the phenotypic differences, as well as a pre-symptomatic diagnostic test to distinguish patients at risk for the overlapping but different clinical features of the disorders. In this study, we collected 19 new JP-HHT patients from which we identified 15 additional SMAD4 mutations. We also reviewed the literature for other reports of JP patients with HHT symptoms with confirmed SMAD4 mutations. Our combined results show that although the SMAD4 mutations in JP-HHT patients do show a tendency to cluster in the MH2 domain, mutations in other parts of the gene also cause the combined syndrome. Thus, any mutation in SMAD4 can cause JP-HHT. Any JP patient with a SMAD4 mutation is, therefore, at risk for the visceral manifestations of HHT and any HHT patient with SMAD4 mutation is at risk for early onset gastrointestinal cancer. In conclusion, a patient who tests positive for any SMAD4 mutation must be considered at risk for the combined syndrome of JP-HHT and monitored accordingly.
机译：青少年息肉病（JP）和遗传性出血性毛细血管扩张（HHT）是由SMAD4和BMPR1A（对于JP）和内皮糖蛋白和ALK1（对于HHT）突变引起的临床上不同的疾病。最近，描述了JP-HHT的综合症，也是由SMAD4的突变引起的。尽管JP和JP-HHT都是由SMAD4突变引起的，但由于JP-HHT患者的所有SMAD4突变都聚集在该蛋白的COOH末端MH2结构域中，因此可能存在基因型：表型相关性。如果有效，则这种相关性将为表型差异提供分子解释，并提供症状前诊断测试以区分有重叠但不同临床特征的风险患者。在这项研究中，我们收集了19名新的JP-HHT患者，从中我们发现了15个另外的SMAD4突变。我们还回顾了文献，以其他有关确诊SMAD4突变的HHT症状JP患者的报道。我们的综合结果表明，尽管JP-HHT患者的SMAD4突变确实显示出在MH2结构域中聚集的趋势，但该基因其他部分的突变也引起了综合症。因此，SMAD4中的任何突变均可引起JP-HHT。因此，任何具有SMAD4突变的JP患者都有HHT内脏表现的风险，任何具有SMAD4突变的HHT患者都有早期发病的胃肠道癌的风险。总之，对于任何SMAD4突变测试呈阳性的患者必须被视为有JP-HHT综合症的风险，并应进行相应监测。

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