目的 分析富脯氨酸跨膜蛋白2（PRRT2）基因突变19例的临床特征和遗传学特点。 方法 回顾性分析2018年1月至2021年7月本院收治的具有PRRT2基因突变的19例患儿家系的临床资料，分析基因突变特点及临床表型。 结果 19个家系先证者均存在PRRT2基因杂合突变，先证者中男13例、女6例。17例患儿的父母一方携带相同突变，2例为新生突变，癫痫发作形式表现为局灶性发作或局灶性发作继发全面性发作和全面性发作。其中15例为碱基重复突变（c.649dupC，p.Arg217Profs*8），2例碱基缺失突变（c.649delC，p.Arg217Glufs*12），1例同时携带有2个致病基因突变（PRRT2，c.649dupC，p.Arg217Profs*8和SPAST基因c.349C>T p.Arg117*），1例无义突变（c.46G>T，p.Glu16*），该变异为未曾报道的新突变。13例患儿诊断为良性家族性婴儿癫痫（BFIE），2例为发作性运动诱发性运动障碍（PKD），2例为良性婴儿癫痫（BIE），2例为婴儿惊厥伴阵发性舞蹈性手足徐动症（ICCA）。 结论 PRRT2基因突变为BFIE、PKD、BIE、ICCA的致病基因。c.649dupC是PRRT2基因的热点突变，c.46G>T为未报道的致病性突变。 Objective To investigate the clinical and genetic characteristics of proline-rich transmenbrane protein 2 (PRRT2) gene mutations in 19 children. Methods The clinical and pedigree data of 19 children with PRRT2 gene mutations admitted to our hospital between January 2018 and July 2021 were retrospectively analyzed for characteristics of the mutation and clinical phenotypes. Results A total of 19 probands from 19 families had heterozygous mutations in the PRRT2 gene. Among the probands, 13 were males and 6 were females. A total of 17 children had one parent carrying the same mutation, while 2 others had de-novo mutations. The patterns of seizure included focal seizures or focal seizures followed by generalized seizures, and generalized seizures. Among them, 15 had base duplication mutations (c.649dupC, p.Arg217Profs*8), 2 had base deletion mutations (c.649delC, p.Arg217Glufs*12), 1 had 2 disease-causing gene mutations (PRRT2, c.649dupC, p.Arg217Profs*8, and SPAST gene c.349C>T p.Arg117*), and 1 had a nonsense mutation (c.46G>T, p.Glu16*) which was novel and previously unreported. Thirteen children were diagnosed with benign familial infantile epilepsy (BFIE), 2 with paroxysmal kinesigenic dyskinesia (PKD), 2 with benign infantile epilepsy (BIE), and 2 with infantile convulsions with paroxysmal choreoathetosis (ICCA) . Conclusion The PRRT2 gene mutations are genetic culprits of BFIE, PKD, BIE and ICCA. Of these, c.649dupC is a hotspot mutation, and c.46G>T is a previously unreported pathogenic mutation.
Abstract
Objective To investigate the clinical and genetic characteristics of proline-rich transmenbrane protein 2 (PRRT2) gene mutations in 19 children. Methods The clinical and pedigree data of 19 children with PRRT2 gene mutations admitted to our hospital between January 2018 and July 2021 were retrospectively analyzed for characteristics of the mutation and clinical phenotypes. Results A total of 19 probands from 19 families had heterozygous mutations in the PRRT2 gene. Among the probands, 13 were males and 6 were females. A total of 17 children had one parent carrying the same mutation, while 2 others had de-novo mutations. The patterns of seizure included focal seizures or focal seizures followed by generalized seizures, and generalized seizures. Among them, 15 had base duplication mutations (c.649dupC, p.Arg217Profs*8), 2 had base deletion mutations (c.649delC, p.Arg217Glufs*12), 1 had 2 disease-causing gene mutations (PRRT2, c.649dupC, p.Arg217Profs*8, and SPAST gene c.349C>T p.Arg117*), and 1 had a nonsense mutation (c.46G>T, p.Glu16*) which was novel and previously unreported. Thirteen children were diagnosed with benign familial infantile epilepsy (BFIE), 2 with paroxysmal kinesigenic dyskinesia (PKD), 2 with benign infantile epilepsy (BIE), and 2 with infantile convulsions with paroxysmal choreoathetosis (ICCA) . Conclusion The PRRT2 gene mutations are genetic culprits of BFIE, PKD, BIE and ICCA. Of these, c.649dupC is a hotspot mutation, and c.46G>T is a previously unreported pathogenic mutation.
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