Background Bardet-Biedl syndrome （BBS） is a genetically heterogeneous disease, and information about BBS in Chinese populations is very limited. The purpose of the present study was to determine the genetic cause of...Background Bardet-Biedl syndrome （BBS） is a genetically heterogeneous disease, and information about BBS in Chinese populations is very limited. The purpose of the present study was to determine the genetic cause of BBS in a Chinese Han family. Methods Clinical data were recorded for the 4-year-old female proband and the available family members. The proband was screened for mutation by Sanger sequencing for a total of 142 exons of the 12 BBS-causing genes （BBS1-BBS12）. The variants detected in the proband were further confirmed in the other family members. Results We identified a novel homozygous nonsense mutation （c.70A〉T, p.K24X） in the BBS4 gene exon 2 in the proband. Such mutant allele was predicted to cause a premature truncation in the N-terminal of the BBS4 protein, and probably induced the nonsense-mediated decay of BBS4 messenger RNAs. The proband＇s parents and brother were heterozygous for the nonsense mutant allele. It was absent in 50 Chinese control subjects. An additional rare heterozygous missense single nucleotide polymorphism （SNP） named rs200718870 in BBS10 gene was also detected in the proband, her father and her brother. Some manifestations of the proband including atypical retinitis pigmentosa, choroidal sclerosis, high myopia, and early onset of obesity might be associated with this mutation in BBS4 gene. The proband＇s father also reported surgical removal of an extra finger during childhood. Conclusions The present study described a novel nonsense mutation in BBS4 gene in a Chinese family. This homozygous mutation was predicted to completely abolish the synthesis of the BBS4 protein. We also detected a rare heterozygous missense SNP in BBSIO gene in the family, but did not find sufficient evidence to support the triallelic inheritance.展开更多
目的研究外周血CD4^(+)CD28^(null)T细胞、肿瘤坏死因子受体超家族成员4(OX40)、4-1BB变化与糖尿病患者动脉粥样硬化(AS)进展的关联性。方法选取2型糖尿病(T2DM)患者120例,根据是否合并AS分为DM-AS组和DM组,比较两组外周血CD4^(+)CD28^(...目的研究外周血CD4^(+)CD28^(null)T细胞、肿瘤坏死因子受体超家族成员4(OX40)、4-1BB变化与糖尿病患者动脉粥样硬化(AS)进展的关联性。方法选取2型糖尿病(T2DM)患者120例,根据是否合并AS分为DM-AS组和DM组,比较两组外周血CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率变化,并根据颈动脉狭窄程度分为轻度AS组(狭窄≤50%)、中度AS组(狭窄51%~69%)及重度AS组(狭窄≥70%),分析CD4^(+)CD28^(null)T细胞、OX40、4-1BB变化与AS进展的关联性。结果120例患者中,DM-AS组有76例,占63.33%;与DM组相比,DM-AS组的DM病程、收缩压、餐后2 h血糖(2 h PG)、糖化血红蛋白、载脂蛋白B、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)水平及CD4^(+)CD28^(null)T细胞亚群比率、OX40阳性比率、4-1BB阳性比率较高,载脂蛋白A1水平较低,差异均有统计学意义(t分别=2.57、2.49、2.78、2.19、3.12、2.94、4.31、5.97、16.91、11.47、-2.52,P均<0.05);CD4^(+)CD28^(null)T细胞、OX40、4-1BB联合诊断DM-AS的曲线下面积(AUC)为0.96。DM-AS组76例中,其中轻度AS组37例、中度AS组29例、重度AS组10例。AS程度与CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率均呈正相关(r分别=0.24、0.48、0.38,P均<0.05)。结论DM-AS患者的外周血CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率均明显升高,对DM-AS具有诊断价值,与AS进展呈正相关。展开更多
文摘Background Bardet-Biedl syndrome （BBS） is a genetically heterogeneous disease, and information about BBS in Chinese populations is very limited. The purpose of the present study was to determine the genetic cause of BBS in a Chinese Han family. Methods Clinical data were recorded for the 4-year-old female proband and the available family members. The proband was screened for mutation by Sanger sequencing for a total of 142 exons of the 12 BBS-causing genes （BBS1-BBS12）. The variants detected in the proband were further confirmed in the other family members. Results We identified a novel homozygous nonsense mutation （c.70A〉T, p.K24X） in the BBS4 gene exon 2 in the proband. Such mutant allele was predicted to cause a premature truncation in the N-terminal of the BBS4 protein, and probably induced the nonsense-mediated decay of BBS4 messenger RNAs. The proband＇s parents and brother were heterozygous for the nonsense mutant allele. It was absent in 50 Chinese control subjects. An additional rare heterozygous missense single nucleotide polymorphism （SNP） named rs200718870 in BBS10 gene was also detected in the proband, her father and her brother. Some manifestations of the proband including atypical retinitis pigmentosa, choroidal sclerosis, high myopia, and early onset of obesity might be associated with this mutation in BBS4 gene. The proband＇s father also reported surgical removal of an extra finger during childhood. Conclusions The present study described a novel nonsense mutation in BBS4 gene in a Chinese family. This homozygous mutation was predicted to completely abolish the synthesis of the BBS4 protein. We also detected a rare heterozygous missense SNP in BBSIO gene in the family, but did not find sufficient evidence to support the triallelic inheritance.
文摘目的研究外周血CD4^(+)CD28^(null)T细胞、肿瘤坏死因子受体超家族成员4(OX40)、4-1BB变化与糖尿病患者动脉粥样硬化(AS)进展的关联性。方法选取2型糖尿病(T2DM)患者120例,根据是否合并AS分为DM-AS组和DM组,比较两组外周血CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率变化,并根据颈动脉狭窄程度分为轻度AS组(狭窄≤50%)、中度AS组(狭窄51%~69%)及重度AS组(狭窄≥70%),分析CD4^(+)CD28^(null)T细胞、OX40、4-1BB变化与AS进展的关联性。结果120例患者中,DM-AS组有76例,占63.33%;与DM组相比,DM-AS组的DM病程、收缩压、餐后2 h血糖(2 h PG)、糖化血红蛋白、载脂蛋白B、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)水平及CD4^(+)CD28^(null)T细胞亚群比率、OX40阳性比率、4-1BB阳性比率较高,载脂蛋白A1水平较低,差异均有统计学意义(t分别=2.57、2.49、2.78、2.19、3.12、2.94、4.31、5.97、16.91、11.47、-2.52,P均<0.05);CD4^(+)CD28^(null)T细胞、OX40、4-1BB联合诊断DM-AS的曲线下面积(AUC)为0.96。DM-AS组76例中,其中轻度AS组37例、中度AS组29例、重度AS组10例。AS程度与CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率均呈正相关(r分别=0.24、0.48、0.38,P均<0.05)。结论DM-AS患者的外周血CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率均明显升高,对DM-AS具有诊断价值,与AS进展呈正相关。
