目的筛查一对同卵双胞胎界限型婴儿重症肌阵挛癫痫（borderland severe myoclonic epilepsy of infancy，SMEB）患儿的钠通道α1（sodium channel α1-subunit，SCN1A）基因并探讨其临床特性。方法总结这对同卵双生子患者的临床特点，应用变性高效液相色谱（denaturing high performance liquid chromatography，DHPLC）技术筛查SCN1A基因全部26个外显子，对发现有异常洗脱峰者再进行直接测序。结果这对孪生姐妹患者均具有典型SMEB的临床特点，她们在SCN1A基因第26号外显子被发现有相同的杂合突变（c．5348C〉T），并导致编码的氨基酸改变（A1783E），为国际上首次发现该位点突变。结论临床表型相似的SMEB同卵双胞胎存在相同位点的SCN1A基因突变，证实SMEB与婴儿重症肌阵挛癫痫同样是基因异常引起的疾病，而且基因与临床表型密切相关。
Objective Cyclic nucleotide phosphodiesterase（PDE）is a critical component of the nitric oxide（NO）signaling pathway and plays critical roles in cognition and learning,Parkinson’s disease,attention deficit hyperactivity disorder, psychosis and depression.The PDEs in the brain of guinea pig have not yet been reported.The present study aimed to detect the unknown Pde cDNAs in the brain of guinea pig.Methods Reverse transcription polymerase chain reaction（RT-PCR）and sequence comparison analysis were performed to detect the expression of Pde cDNAs and to assess the identity rates of cDNA and amino acid sequences between guinea pig and human or mouse,respectvely.The RT-PCR primers were located on the conserved region of human PDE and mouse Pde cDNAs.Results Eleven novel Pde cDNAs were detected in the brain of guinea pig（Cavia porcellus）,including CpPde1a,CpPde1b,CpPde2a,CpPde4a,CpPde4d,CpPde5a,CpPde6c,CpPde7b, CpPde8a,CpPde9a,and CpPde10a.The identity rates of the Pde cDNA sequences between guinea pig and human ranged from 83.8%to 94.3%,and those of the amino acid sequences ranged from 91.9%to 100%.The identity rates of Pde cDNA sequences between guinea pig and mouse ranged from 84.6%to 92.1%,and those of amino acid sequences ranged from 91.2% to 99.2%.The average identity rate of the 11 Pde cDNA sequences between guinea pig and human was significantly higher（P 0.01）than that between guinea pig and mouse.The putative partial amino acid sequences of guinea pig contained at least one of the conserved domains of human and mouse PDE proteins.Conclusion These results indicate that the brainexpressed Pde genes are identified in guinea pig,which lays the foundation for further investigating the physiological roles of PDE proteins in the brain.
