GPR98基因突变的癫痫患儿临床表型与神经发育商的研究

Analysis of the clinical phenotype and neurological developmental quotient in children with epilepsy and GPR98 gene mutation

目的 探讨GPR98基因突变癫痫患儿的基因型、临床表型及神经发育商之间的关系.方法 收集65个癫痫家系先证者及家系成员的临床资料和外周血标本,应用二代测序加目标区域靶向捕获技术和PCR产物直接测序技术进行癫痫基因突变筛查及验证,分析临床表型、基因型以及神经发育商的关系.结果 65个癫痫家系中发现了7例先证者存在新GPR98基因突变位点,分别为杂合错义变异c.6083C>T、c.1969A>C、c.17531C >T、c.9069G>C、c.6661G>A和c.18496A>C以及无义变异c.14224G>T,且其父母亲其中一方携带与先证者相同的GPR98基因点突变.在7例GPR98基因突变的先证者中,6例患儿均以无热性惊厥为初始症状,1例发病初期表现为热性惊厥,发作形式表现为全面性发作为主.进一步采用Gesell发育量表对7例GPR98基因突变癫痫患儿及30例正常儿童进行发育商测试,结果 提示GPR98基因突变癫痫患儿的5个能区及总体神经发育商平均值分别比正常儿童差,差异均有统计学意义(P<0.01).结论 GPR98基因突变患儿的癫痫发作形式以全面性发作为主,其精神运动发育迟缓可能与GPR98基因突变有关.

Objective To study the relation between the clinical phenotype and neurological developmental quotient in children with epilepsy and GPR9&gene mutation.Methods Genomic DNA was extracted from peripheral blood lymphocytes of the probands and other available members in the epilepsy families.Clinical datas and screened for mutations by next-generation sequencing conbined target sequencing technology and PCR and direct DNA sequencing were collected.Then,the relations between the clinical phenotype and developmental quotient in children with epilepsy and GPR98 gene mutation was analyzed.Results Seven novel GPR9&gene mutations were found in seven probands in 65 families,including six heterozygote missense mutations(c.6083C>T,c.1969A>Cxc.17531C>T,e.9069G>Cxe.6661G>A and c.18496A>C)and one nonsense mutation(c.14224G>T).One of their parents carried the same GPR98 gene mutation as the proband’s.The initial symptom of six cases was afebrile seizures and one showed febrile seizure,in which the main type seizure was generalized seizure.Moreover,was were significant difference between children with epilepsy and GPR9%gene mutations and healthy children in developmental quotient lest(P<0.01).Conclusions The main type of seizures in children with epilepsy and GPR9Z gene mutations is generalized seizure.Furthermore,GPU98 gene mutations may be associated with psychomotor retardation.