摘要
目的总结结节性硬化症(TSC)的临床特征及遗传学病因。方法回顾性分析2018年1月及4月郑州大学附属儿童医院神经内科收治的基因诊断明确的2个TSC家系,归纳其临床表现和辅助检查结果,通过对先证者及家系成员进行全外显子组测序和家系突变验证,查明遗传学病因。结果2个家系先证者分别为1岁7月女性、2岁4月龄男性;出生时均正常,学龄前期出现癫痫发作。先证者的姐、妹及母亲均出现多块散在色素脱失斑,无癫痫发作;父亲表型均正常。2名先证者及部分家系成员头颅CT示颅内多发钙化影,MRI提示脑实质皮层下及双侧侧脑室旁多发异常信号。先证者1及姐姐、母亲为TSC2基因c.5024 C>T(p.Pro1675Leu)错义杂合突变,心脏、肝脏、双肾彩超提示存在错构瘤,双肾实质内囊性暗区。先证者2及妹妹、母亲为TSC1基因c.737+1(IVS8)G>A移码杂合变异,内脏器官无错构瘤。结论TSC临床表现中癫痫发作常见,可出现皮肤异常改变,以及累及头颅、心脏、肝脏、肾脏等多部位的错构瘤;致病基因为TSC2时患者临床表型较重。
Objective To summarize the clinical features and genetic etiology of tuberous sclerosis(TSC).Methods A retrospective analysis was carried out to identify the clinical features and auxiliary examination reults of TSC patients in 2 pedigrees admitted to our hospital from January 2018 to April 2018.Whole exome sequencing was performed in peripheral blood samples from these patients and the mutations in their parents were validated by Sanger sequencing.Results The two probands were a one-year and 7-month old girl and a 2-year and 4-month old boy.They were all normal at birth and had epileptic seizures at preschool age.The elder sister,younger sister and mother of the probands showed abnormal skin and no seizures,and the father had normal phenotype.Physical examination showed normal mental and motor development,facial angiofibroma and depigmentation spots on the skin,knots and shark-like spots on part of the skin,and multiple intracranial calcification shadows on head CT;MR imaging revealed multiple abnormal signals under the parenchymal cortex and bilateral lateral ventricles.The proband(1)and her sister carried heterozygous missense mutation c.5024 c>T(p.pro1675leu)in TSC2 gene;ultrasound of heart,liver and kidney showed presence of hamartoma and cystic scotoma in renal parenchyma.The proband(2)and his younger sister carried heterozygosous splicing variation c.737+1(IVS8)G>A in TSC1 gene,inherited from his mother;the head CT of younger sister was normal,and there was no hamartoma in the younger sister and the mother's internal organs.Conclusions TSC is characterized by epileptic seizures and abnormal skin changes in preschool age.It may involve multiple hamartomas of skull,heart,liver,kidney,or other internal organs.The mutation frequency of TSC2 gene is higher than that of TSC1 gene,and the clinical phenotype is severe.
作者
梅道启
梅世月
王潇娜
陈晓轶
王媛
陈国洪
张耀东
王营
董世杰
Mei Daoqi;Mei Shiyue;Wang Xiaona;Chen Xiaoyi;Wang Yuan;Chen Guohong;Zhang Yaodong;Wang Ying;Dong Shijie(Department of Neurology,Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital/Zhengzhou Children's Hospital,Zhengzhou 450018,China;Henan Provincial Key Laboratory of Children Genetics and Metabolic Diseases/Henan Engineering Research Center of Childhood Neurodevelopment,Zhengzhou 450018,China)
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2020年第10期1040-1043,共4页
Chinese Journal of Neuromedicine
基金
国家自然科学基金(81701125)
河南省科技攻关项目(2018020633、2018020603)
河南省儿童神经发育工程研究中心开放课题(SG201907)。
关键词
结节性硬化症
基因突变
癫痫
Tuberous sclerosis
Gene mutation
Epilepsy
