一例结节性硬化症患者的临床表型和TSC基因突变分析

Analysis of TSC gene mutation in a patient with tuberous sclerosis

目的检测1例结节性硬化症患者TSCl、TSC2基因突变情况，探讨其分子发病机制。方法收集1例结节性硬化症患者的临床表型资料，提取患者及其4名家系成员（父母、舅舅、丈夫）的外周血DNA，应用PCR反应扩增TSCl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。结果患者面部血管纤维瘤、前额纤维斑20年，后腰鲨革样斑10年，伴智力障碍，无癫痫发作史。测序结果显示患者在TSC2基因第34外显子第4258位与4261位碱基之间缺失了TCAG4个碱基，为c．4258—4261delTCAG（P．Serl420GlyfsX55）移码突变。在4名表型正常家系成员及100名正常对照中均未检测到该位点突变。结论TSC2基因第34外显子c．4258-4261delTCAG（p．Serl420GlyfsX55）移码突变可能是该结节性硬化症患者发病的原因。

Objective To identify pathogenic mutation of the TSC1 and TSC2 genes in a patient with tuberous sclerosis. Methods Peripheral venous blood samples and clinical data of a pregnant woman with tuberous sclerosis and 4 family members （parents, uncle and husband） were collected. Genomic DNA was extracted. All coding exons of the TSC1 and TSC2 genes and their flanking intronic sequences were amplified by polymerase chain reaction and subjected to direct sequencing. Results The patient has presented facial angiofibroma and prefrons fibrous plaque for 20 years, and lumbar connective tissue nevus for 10 years. She also had mental retardation but no epilepsy. A novel frame-shift mutation c. 4258- 4261delTCAG was detected in exon 34 of the TSC2 gene, which had led to a premature stop codon TAG after the 55th amino acids. The same mutation was not found in the unaffected family members and 100 unrelated healthy controls. Conclusion The novel frameshifting mutation c. 4258-4261delTCAG （p. Ser1420GlyfsX55） in the TSC2 gene may be responsible for the disease in the patient.