【作者】 孙贺东；

【导师】 资晓宏；

【作者基本信息】 中南大学 ， 神经病学， 2008， 硕士

【摘要】 背景:原发性红斑肢痛症(primary erythermalgia,PETA)是一种罕见的常染色体显性遗传病,主要表现为不同程度的阵发的四肢末端灼痛,伴肢末端皮肤发红,常由运动或温度变化诱发或加重,疾病发作时患肢处于低温环境可使症状缓解或减轻。目前致病机理不清,尚无特效的治疗方法,该病给患者及其家人身心带来严重的伤害。有研究将PETA致病基因定位于2q24.1～24.3,并发现该区间内的SCN9A基因为该病的致病基因。SCN9A基因突变的致病机制正在研究中。亦有研究在一些PETA家系的中未检测到SCN9A外显子突变,提示PETA有遗传异质性,寻找新的PETA致病基因进而研究其致病机制成为目前科研的热点。目的:求证一湖南PETA家系是否具有新的致病基因,探讨新的致病基因位点是否位于2q24.1～24.3的D2S1353～D2S1776区间。方法与结果:对一湖南PETA家系进行了调查,收集足够的家系资料,以便进行家系连锁分析得到有意义的LOD值。对该家系先症者进行SCN9A基因全部26个外显子正反向测序,未发现SCN9A异常突变,进而在2q24.1～24.3选取6个微卫星标记(STR),在部分家系成员中作连锁分析,排除该PETA家系致病基因定位于2q24.1～24.3的D2S1353～D2S1776区间。结论:该湖南PETA家系不存在SCN9A基因外显子突变,提示有新的致病基因,新致病基因位点不在D2S1353～D2S1776区间。更多还原

【Abstract】 Backgrounds: Primary erythromelalgia (PETA) is a rare disease act as autosomal dominant inheritance, characteristic mainly for the burning sensation of different levels of the end of limbs with the end of limb skin redness, often induced by the movement or temperature changes. Symptoms relief when expose to a low temperature environment such as cool water. The pathogenic mechanism is unclear, and there is no effective cure it by now. PETA bring serious physical and mental harm to patients and their family members. Some studies have mapped its virulence gene to 2q24.1～24.3, and found SCN9A is the virulence gene. The pathogenic mechanisms of SCN9A mutation is under studying. But in some PETA family, SCN9A mutation was not detected, suggesting genetic heterogeneity of PETA. Then searching for a new virulence gene become a research hot.Obectives: To identify whether the PETA family of HUNAN has new disease gene and whether the gene loci is in 2q24.1～24.3.Methods and results: We investigated the PETA family of HUNAN CHINA, gathered enough information for linkage analysis, in order to get a meaningful LOD score.We sequenced all 26 exons of SCN9A gene of the proband by obverse and reverse trend, and didn’t find meaningful mutation, then selected 6 microsatellite markers (STR) in 2q24.1～24.3 and did linkage analysis in some of the family members, fond out that no linkage exists between PETA and D2S1353～D2S1776, ruled out the virulence gene locate in this range.Conclusion: There is no SCN9A gene mutation in HUNAN PETA family, indicating new pathogenic gene. The new pathogenic gene loci is not in D2S1353～D2S1776.更多还原