AIM: To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn’s disease (CD). METHODS...AIM: To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn’s disease (CD). METHODS: A cohort of 19 unrelated pediatric and 55 unrelated adult patients with Crohn’s disease and 49 healthy controls were studied. Genotyping of the three common CD-associated CARD15 variants (Arg702Trp, Gly908Arg and 1007finsC changes) with the SLC22A4 1672C→T, and SLC22A5 -207G→C mutations was performed by direct sequencing of the specifi c regions of these genes.RESULTS: At least one CARD15 mutation was present in 52.6% of the children and in 34.5% of the adults compared to 14.3% in controls. Surprisingly, strongly different mutation profi le was detected in the pediatric versus adult patients. While the G908R and 1007finsC variants were 18.4% and 21.1% in the pediatric group, they were 1.82% and 11.8% in the adults, and were 1.02% and 3.06% in the controls, respectively. The R702W allele was increased approximately two-fold in the adult subjects, while in the pediatric group it was only approximately 64% of the controls (9.09% in the adults, 2.63% in pediatric patients, and 4.08% in the controls). No accumulation of the OCTN variants was observed in any patient group versus the controls.CONCLUSION: The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high and the profile differs from the adult CD patients, whereas the results for SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD.展开更多
目的分析海南省少数民族地区新生儿原发性肉碱缺乏症(primary carnitine deficiency,PCD)筛查情况及溶质载体家族22A5(solute carrier family 22 member 5,SLC22A5)基因突变特点。方法通过液相(色谱)串联质谱分析技术对2014年6月至2016...目的分析海南省少数民族地区新生儿原发性肉碱缺乏症(primary carnitine deficiency,PCD)筛查情况及溶质载体家族22A5(solute carrier family 22 member 5,SLC22A5)基因突变特点。方法通过液相(色谱)串联质谱分析技术对2014年6月至2016年6月海南省8个少数民族自治市县52403例新生儿血氨基酸谱、游离肉碱(free carnitine,C0)及酰基肉碱进行检测,召回PCD初筛可疑阳性的新生儿及其母亲复查,分析确诊PCD新生儿及PCD母亲所生新生儿的血酰基肉碱谱动态变化,采用Sanger测序法结合MassArray技术测定确诊病例的SLC22A5基因突变位点,对PCD新生儿补充左卡尼汀治疗,随访,观察患儿发育情况。结果海南省8个少数民族市县2年期间检出PCD新生儿8例,发病率为1/6550;PCD母亲12例,发病率为1/4367;PCD新生儿组初筛时C0、(C3+C16)水平与PCD母亲所生新生儿组相比,差异无统计学意义(P>0.05);PCD新生儿组复筛时C0、(C3+C16)水平均比初筛时降低(P<0.05);PCD母亲所生新生儿组复筛时C0水平比初筛时增高,(C3+C16)水平均比初筛时降低(P<0.05);PCD新生儿检出8种变异,最常见的是c.1400C>G(p.S467C)、c.51C>G(p.F17)、c.760C>T(p.R254X);1种为新发突变,为c.1380C>A(p.N460K)。PCD母亲检出7种变异,最常见的是c.1400C>G(p.S467C)、c.51C>G(p.F17L)、c.1195C>T(p.R399W),1例重型变异c.760C>T(p.R254X);8例PCD均接受左卡尼汀治疗,预后良好,但终止治疗可诱发不良事件。结论海南省8个少数民族市县新生儿PCD发病率较高,液相(色谱)串联质谱分析技术可有效检出PCD,增加多种酰基肉碱量化指标(C3+C16)可提升筛查性能;c.1400C>G(p.S467C)、c.51C>G(p.F17)可能成为海南省少数民族地区新生儿PCD的SLC22A5基因热点突变类型;左卡尼汀治疗效果好,预后良好。展开更多
基金Supported by the grant of Hungarian Science Foundation No. OTKA T 49589
文摘AIM: To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn’s disease (CD). METHODS: A cohort of 19 unrelated pediatric and 55 unrelated adult patients with Crohn’s disease and 49 healthy controls were studied. Genotyping of the three common CD-associated CARD15 variants (Arg702Trp, Gly908Arg and 1007finsC changes) with the SLC22A4 1672C→T, and SLC22A5 -207G→C mutations was performed by direct sequencing of the specifi c regions of these genes.RESULTS: At least one CARD15 mutation was present in 52.6% of the children and in 34.5% of the adults compared to 14.3% in controls. Surprisingly, strongly different mutation profi le was detected in the pediatric versus adult patients. While the G908R and 1007finsC variants were 18.4% and 21.1% in the pediatric group, they were 1.82% and 11.8% in the adults, and were 1.02% and 3.06% in the controls, respectively. The R702W allele was increased approximately two-fold in the adult subjects, while in the pediatric group it was only approximately 64% of the controls (9.09% in the adults, 2.63% in pediatric patients, and 4.08% in the controls). No accumulation of the OCTN variants was observed in any patient group versus the controls.CONCLUSION: The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high and the profile differs from the adult CD patients, whereas the results for SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD.
文摘目的分析海南省少数民族地区新生儿原发性肉碱缺乏症(primary carnitine deficiency,PCD)筛查情况及溶质载体家族22A5(solute carrier family 22 member 5,SLC22A5)基因突变特点。方法通过液相(色谱)串联质谱分析技术对2014年6月至2016年6月海南省8个少数民族自治市县52403例新生儿血氨基酸谱、游离肉碱(free carnitine,C0)及酰基肉碱进行检测,召回PCD初筛可疑阳性的新生儿及其母亲复查,分析确诊PCD新生儿及PCD母亲所生新生儿的血酰基肉碱谱动态变化,采用Sanger测序法结合MassArray技术测定确诊病例的SLC22A5基因突变位点,对PCD新生儿补充左卡尼汀治疗,随访,观察患儿发育情况。结果海南省8个少数民族市县2年期间检出PCD新生儿8例,发病率为1/6550;PCD母亲12例,发病率为1/4367;PCD新生儿组初筛时C0、(C3+C16)水平与PCD母亲所生新生儿组相比,差异无统计学意义(P>0.05);PCD新生儿组复筛时C0、(C3+C16)水平均比初筛时降低(P<0.05);PCD母亲所生新生儿组复筛时C0水平比初筛时增高,(C3+C16)水平均比初筛时降低(P<0.05);PCD新生儿检出8种变异,最常见的是c.1400C>G(p.S467C)、c.51C>G(p.F17)、c.760C>T(p.R254X);1种为新发突变,为c.1380C>A(p.N460K)。PCD母亲检出7种变异,最常见的是c.1400C>G(p.S467C)、c.51C>G(p.F17L)、c.1195C>T(p.R399W),1例重型变异c.760C>T(p.R254X);8例PCD均接受左卡尼汀治疗,预后良好,但终止治疗可诱发不良事件。结论海南省8个少数民族市县新生儿PCD发病率较高,液相(色谱)串联质谱分析技术可有效检出PCD,增加多种酰基肉碱量化指标(C3+C16)可提升筛查性能;c.1400C>G(p.S467C)、c.51C>G(p.F17)可能成为海南省少数民族地区新生儿PCD的SLC22A5基因热点突变类型;左卡尼汀治疗效果好,预后良好。
