结节性硬化1例报道及临床表型文献复习

report of one case and literature review of clinical phenotype

摘要:

目的：检测一结节性硬化家系TSC1、TSC2基因突变情况,总结该突变类型临床表型。方法：收集1结节性硬化患者临床表型资料,提取患者父母的外周血DNA,应用PCR反应扩增TSC1和TSC2基因所有的外显子编码区及其侧翼序列,通过对PCR反应产物直接测序进行序列分析。进一步总结国内外目前报道过的该突变位点的临床表型。结果：患者右腰部、左腘窝及面颊部血管纤维瘤20余年,局灶性癫痫,不伴智力障碍。测序结果显示患者在TSC2基因第14外显子第1513位C突变为T。在其父母亲及25名正常对照中均未检测到该位点突变。检索国内外报道的该突变位点的患者临床表型进行总结分析,发现该位点突变的患者均有皮肤和癫痫,发病年龄和性别无明显特异性。结论 TSC2基因第14号外显子C1513C>T无义突变可能是该结节性硬化症患者发病的原因,该突变位点临床表现多样。

Abstract:

objective To identify pathogenic mutation of the TSC1 and TSC2 genes in a family with tuberous sclerosis, and to analyze clinical data of this mutation. Methods Peripheral venous blood samples and clinical data of the patients and her parents were collected. Genomic DNA was extracted. All coding exons of the TSC1 and TSC2 genes were amplified by polymerase chain reaction and subjected to direct sequencing. The clinical data of all patients with this mutation in internal reports were concluded. Result The patient has presented angiofibroma of the right waists, left popliteal fossa and face for more than twenty years. She also had epilepsy but no mental retardation. A nosense mutation was c.1513C>T was detected in exon 14 of the TSC2 gene, which had led to a premature stop eodon TAG after the 505th amino acids.The same mutation was not found in her parents and 25 unrelated healthy controls. Conclusion The nosense mutation c.1513C>T in the TSC2 gene may be responsible for the disease in the patients and the clinical phenotype of this mutation was very diverse.