目的探索肌萎缩侧索硬化症(ALS)中编码结合泛素并调节核因子激活信号通路多功能蛋白(SQSTM1)基因突变患者的表型特征。方法对15例家族性ALS(FALS)先证者和275例散发性ALS(SALS)患者SQSTM1全部外显子进行二代测序,所得变异根据美国ACMG...目的探索肌萎缩侧索硬化症(ALS)中编码结合泛素并调节核因子激活信号通路多功能蛋白(SQSTM1)基因突变患者的表型特征。方法对15例家族性ALS(FALS)先证者和275例散发性ALS(SALS)患者SQSTM1全部外显子进行二代测序,所得变异根据美国ACMG指南进行致病性分析,检索Pubmed、Medline及Web of Science文献数据库中已报道的SQSTM1突变的ALS患者,对SQSTM1突变的ALS患者的表型进行综述。结果(1)290例中,3例SALS患者分别携带1个SQSTM1杂合错义突变,即c.653G>A,p.G218D、c.655G>A,p.A219T和c.923C>T,p.P308L。其中c.923C>T,p.P308L为已报道的致病突变,患者临床表现为单纯ALS不伴认知功能障碍,其他2个位点为非致病性。(2)检索数据库并进行文献综述,共发现71例SQSTM1突变的ALS患者。SQSTM1基因在FALS的突变率约2.70%,其中高加索人群2.89%,亚洲人群尚未见报道;SQATM1基因在SALS的突变率约1.3%,其中高加索人群1.5%,亚洲人群1.09%。SQSTM1突变主要有错义突变(66/71)、剪切突变(2/71)、内含子缺失(1/71)和缺失突变(2/71)。71例中有56例具有详细临床表型,其中经典ALS 22例、进行性延髓麻痹(PBP)11例、连枷臂综合征(FAS)2例、连枷腿综合征(FLS)7例、进行性脊肌萎缩症(PMA)2例,共患额颞叶痴呆(FTD)/帕金森病(PD)、佩吉特氏骨病(PDB)7例。从突变方式看,剪切突变的临床表型相对较轻、生存期较长,经典ALS的临床表型异质性大。SQSTM1高频突变位点是p.A33V(7/71)、p.K238E(6/71)、p.L238G(7/71)和p.P392L(7/71),同一位点的临床表型差异也很大。结论SQSTM1在家族性、散发性ALS中以及不同种族中的突变率存在差异,其临床表型异质性较大;SQSTM1突变可导致多系统蛋白病(MSP)。本研究发现1例ALS携带SQSTM1基因突变,该位点(p.P308L)在ALS中为首次报道。展开更多
Objective To investigate the association between quality of life （QOL） and sociodemographic factors, clinical seizure factors, depression and anxiety in patients suffering from epilepsy. Methods We examined 141 cons...Objective To investigate the association between quality of life （QOL） and sociodemographic factors, clinical seizure factors, depression and anxiety in patients suffering from epilepsy. Methods We examined 141 consecutive patients with epilepsy （mean age 25.8＋9.6, 61.7% male）. All patients completed the Self-Rating Depression Scale, Self-Rating Anxiety Scale , WHOQOL-BREF and O, OLIE-31（Chinese version）. Multiple linear regression analyses were applied to investigate factors impact on O.OL. Results The results revealed that scores on two domains of the WHOO.OL-BREF （i.e., physical and psychological domains, P〈O.05） were significantly lower in the epilepsy group compared with the control group. Multiple regression analyses showed that anxiety, depression and course explained approximately 40% of the variance in patients＇ QOL. Anxiety was consistently the strongest predictor of lower scores on almost all QOL domains. In addition, the severity of depressive symptoms was significantly associated with lower scores across many QOL domains. Conclusion Our findings suggest that QOLIE scores might be substantially affected by the presence and severity of anxiety symptoms and, to a lesser degree, of depressive symptoms and prolonged course of illness. In contrast, clinical seizure variables had a weaker association with QOL Healthcare professionals should be aware of the significance of patients＇ emotional state and of the role it plays in their O, OL.展开更多
文摘目的探索肌萎缩侧索硬化症(ALS)中编码结合泛素并调节核因子激活信号通路多功能蛋白(SQSTM1)基因突变患者的表型特征。方法对15例家族性ALS(FALS)先证者和275例散发性ALS(SALS)患者SQSTM1全部外显子进行二代测序,所得变异根据美国ACMG指南进行致病性分析,检索Pubmed、Medline及Web of Science文献数据库中已报道的SQSTM1突变的ALS患者,对SQSTM1突变的ALS患者的表型进行综述。结果(1)290例中,3例SALS患者分别携带1个SQSTM1杂合错义突变,即c.653G>A,p.G218D、c.655G>A,p.A219T和c.923C>T,p.P308L。其中c.923C>T,p.P308L为已报道的致病突变,患者临床表现为单纯ALS不伴认知功能障碍,其他2个位点为非致病性。(2)检索数据库并进行文献综述,共发现71例SQSTM1突变的ALS患者。SQSTM1基因在FALS的突变率约2.70%,其中高加索人群2.89%,亚洲人群尚未见报道;SQATM1基因在SALS的突变率约1.3%,其中高加索人群1.5%,亚洲人群1.09%。SQSTM1突变主要有错义突变(66/71)、剪切突变(2/71)、内含子缺失(1/71)和缺失突变(2/71)。71例中有56例具有详细临床表型,其中经典ALS 22例、进行性延髓麻痹(PBP)11例、连枷臂综合征(FAS)2例、连枷腿综合征(FLS)7例、进行性脊肌萎缩症(PMA)2例,共患额颞叶痴呆(FTD)/帕金森病(PD)、佩吉特氏骨病(PDB)7例。从突变方式看,剪切突变的临床表型相对较轻、生存期较长,经典ALS的临床表型异质性大。SQSTM1高频突变位点是p.A33V(7/71)、p.K238E(6/71)、p.L238G(7/71)和p.P392L(7/71),同一位点的临床表型差异也很大。结论SQSTM1在家族性、散发性ALS中以及不同种族中的突变率存在差异,其临床表型异质性较大;SQSTM1突变可导致多系统蛋白病(MSP)。本研究发现1例ALS携带SQSTM1基因突变,该位点(p.P308L)在ALS中为首次报道。
文摘Objective To investigate the association between quality of life （QOL） and sociodemographic factors, clinical seizure factors, depression and anxiety in patients suffering from epilepsy. Methods We examined 141 consecutive patients with epilepsy （mean age 25.8＋9.6, 61.7% male）. All patients completed the Self-Rating Depression Scale, Self-Rating Anxiety Scale , WHOQOL-BREF and O, OLIE-31（Chinese version）. Multiple linear regression analyses were applied to investigate factors impact on O.OL. Results The results revealed that scores on two domains of the WHOO.OL-BREF （i.e., physical and psychological domains, P〈O.05） were significantly lower in the epilepsy group compared with the control group. Multiple regression analyses showed that anxiety, depression and course explained approximately 40% of the variance in patients＇ QOL. Anxiety was consistently the strongest predictor of lower scores on almost all QOL domains. In addition, the severity of depressive symptoms was significantly associated with lower scores across many QOL domains. Conclusion Our findings suggest that QOLIE scores might be substantially affected by the presence and severity of anxiety symptoms and, to a lesser degree, of depressive symptoms and prolonged course of illness. In contrast, clinical seizure variables had a weaker association with QOL Healthcare professionals should be aware of the significance of patients＇ emotional state and of the role it plays in their O, OL.
