Nocturnal frontal lobe epilepsy up to now has been considered a channelopathy caused by mutations in the α 4 and β 2 subunits of the neuronal nicotinic acetylcholine receptor. However, these mutations account for on...Nocturnal frontal lobe epilepsy up to now has been considered a channelopathy caused by mutations in the α 4 and β 2 subunits of the neuronal nicotinic acetylcholine receptor. However, these mutations account for only a minority of patients, and the existence of at least a new locus for the disease has been demonstrated. In one Italian nocturnal frontal lobe epilepsy family, we identified two new putative loci on chromosomes 3 and 8, where several candidate genes are mapped. In particular, on chromosome 8, corticotropin-releasing hormone gene (CRH) appears to be a good candidate. We therefore searched for CRH mutations in the proband. The study allowed the identification of a nucle-otide variation in the promoter that was subsequently detected in all affected and obligate carrier members of the same family, in two sporadic cases, in all affected members of an additional compliant family, and in the proband of a noncompliant family. Moreover, a different mutation in the promoter was detected in a familial case. In vitro experiments showed altered levels of gene expression. CRH alterations could explain several autosomal dominant nocturnal frontal lobe epilepsy clinical features.展开更多
目的探讨促肾上腺皮质激素释放因子受体1(CRHR1)基因rs4458044位点多态性与新生儿持续性肺动脉高压(PPHN)的相关性.方法采用引物入侵分析技术检测2012年3月至2018年3月济宁医学院附属医院收治的临床确诊为PPHN的85例患儿和50例健康照组...目的探讨促肾上腺皮质激素释放因子受体1(CRHR1)基因rs4458044位点多态性与新生儿持续性肺动脉高压(PPHN)的相关性.方法采用引物入侵分析技术检测2012年3月至2018年3月济宁医学院附属医院收治的临床确诊为PPHN的85例患儿和50例健康照组的血液样本的基因多态性,对2组研究对象的一般临床资料、临床指标和CRHR1基因(rs4458044)多态性采用t检验和x2检验进行统计分析.结果PPHN组和健康对照组在性别、胎龄、出生体质量和1 min Apgar评分上差异均无统计学意义(均P>0.05),而在辅助通气时间和最高氧合指数上差异均有统计学意义(均P<0.05).CRHR1基因(rs4458044)GG、CG和CC基因型在PPHN组和健康对照组的频率分别为2.35%、43.53%、54.12%和50.00%、38.00%、12.00%,CG/CC基因型在PPHN组的频率显著高于健康对照组(P<0.05),CG/CC基因型患儿出现PPHN的风险度高于GG基因型,以GG基因型为参照(CG基因型,OR=24.34,95%CI:5.20~113.87,P=0.00;CC基因型,OR=95.83,95%CI:17.99~510.49,P=0.00),携带C等位基因的新生儿辅助通气时间和最高氧合指数显著高于未携带C等位基因的新生儿(P<0.05).结论CRHR1基因(rs4458044)多态性与PPHN相关.展开更多
文摘Nocturnal frontal lobe epilepsy up to now has been considered a channelopathy caused by mutations in the α 4 and β 2 subunits of the neuronal nicotinic acetylcholine receptor. However, these mutations account for only a minority of patients, and the existence of at least a new locus for the disease has been demonstrated. In one Italian nocturnal frontal lobe epilepsy family, we identified two new putative loci on chromosomes 3 and 8, where several candidate genes are mapped. In particular, on chromosome 8, corticotropin-releasing hormone gene (CRH) appears to be a good candidate. We therefore searched for CRH mutations in the proband. The study allowed the identification of a nucle-otide variation in the promoter that was subsequently detected in all affected and obligate carrier members of the same family, in two sporadic cases, in all affected members of an additional compliant family, and in the proband of a noncompliant family. Moreover, a different mutation in the promoter was detected in a familial case. In vitro experiments showed altered levels of gene expression. CRH alterations could explain several autosomal dominant nocturnal frontal lobe epilepsy clinical features.
文摘目的探讨促肾上腺皮质激素释放因子受体1(CRHR1)基因rs4458044位点多态性与新生儿持续性肺动脉高压(PPHN)的相关性.方法采用引物入侵分析技术检测2012年3月至2018年3月济宁医学院附属医院收治的临床确诊为PPHN的85例患儿和50例健康照组的血液样本的基因多态性,对2组研究对象的一般临床资料、临床指标和CRHR1基因(rs4458044)多态性采用t检验和x2检验进行统计分析.结果PPHN组和健康对照组在性别、胎龄、出生体质量和1 min Apgar评分上差异均无统计学意义(均P>0.05),而在辅助通气时间和最高氧合指数上差异均有统计学意义(均P<0.05).CRHR1基因(rs4458044)GG、CG和CC基因型在PPHN组和健康对照组的频率分别为2.35%、43.53%、54.12%和50.00%、38.00%、12.00%,CG/CC基因型在PPHN组的频率显著高于健康对照组(P<0.05),CG/CC基因型患儿出现PPHN的风险度高于GG基因型,以GG基因型为参照(CG基因型,OR=24.34,95%CI:5.20~113.87,P=0.00;CC基因型,OR=95.83,95%CI:17.99~510.49,P=0.00),携带C等位基因的新生儿辅助通气时间和最高氧合指数显著高于未携带C等位基因的新生儿(P<0.05).结论CRHR1基因(rs4458044)多态性与PPHN相关.
