TSC2/PKD1邻接基因综合征临床表型与基因分析

Clinical phenotype and gene analysis of TSC2/PKD1 adjacency gene syndrome

目的探讨1例TSC2/PKD1邻接基因综合征患儿的临床表型及基因特点,提高临床对本病的认识。方法回顾性分析郑州大学附属儿童医院神经内科确诊的1例TSC2/PKD1邻接基因综合征患儿,总结患儿的临床资料、实验室检查、影像学特点及基因变异特点。结果患儿女性,为17个月幼儿,以"间断性抽搐伴发育落后17个月"为主诉就诊。临床表现为癫痫发作,发作形式为成串痉挛发作、失神发作、局灶性发作,躯干部及颈部可见色素脱失斑,头颅磁共振成像提示双侧大脑半球部分皮质及皮质下多发斑片状信号,双侧侧脑室室管膜下多发小结节状影,心脏彩色超声提示卵圆孔未闭、心包积液,腹部彩色超声提示多囊肾。眼科彩色超声示左眼视盘周围见局限性团状小隆起病变。家系全外显子基因测序示先证者在染色体位置chr16∶2125799-2185690中的TSC2基因存在部分缺失(NM_(0)00548),应用实时定量基因扩增荧光检测系统验证为23~42号外显子缺失,PKD1基因外显子全部缺失(NM_(0)01009944),经多重连接探针扩增技术验证为第1~46号外显子缺失,未见下游基因缺失,整体缺失片段大小约为60 kb,患儿父母表型均正常,为野生型。结论 TSC2/PKD1邻接基因综合征相对罕见,可兼具结节性硬化/常染色体显性多囊肾病的临床表现,多数患者神经系统及肾脏受累程度重,预后不良,TSC2/PKD1基因缺失变异为TSC2/PKD1邻接基因综合征的遗传学病因。

Objective To explore the clinical phenotype and gene characteristics of a case of TSC2/PKD1 adjacency gene syndrome,so as to improve the clinical understanding of the disease.Methods A case of TSC2/PKD1 adjacency gene syndrome diagnosed in the Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University was analyzed retrospectively.The clinical data,laboratory examination,imaging characteristics and gene variation characteristics of the child were summarized.Results The patient was a 17 months old girl,with the main complaint of"intermittent convulsion with 17 months of underdevelopment".The clinical manifestations were epileptic seizures,which were in the form of a series of spastic seizures,absence seizures,focal seizures,and depigmentation spots can be seen in the trunk and neck.Cranial magnetic resonance imaging showed multiple patchy signals in the cortex and subcortical areas of the bilateral cerebral hemispheres,multiple small nodular shadows under the ependyma of the bilateral lateral ventricles,the heart color Doppler ultrasound showed patent foramen ovale and pericardial effusion,and the abdomen color Doppler ultrasound showed polycystic kidney.Ophthalmic color Doppler ultrasound showed that there were localized small swelling lesions around the optic disc of the left eye.The whole exon gene sequencing of the pedigree showed the proband had partial deletion of TSC2 gene(NM_000548)at chromosome position chr16:2125799-2185690.The real-time quantitative detection system verified that exons 23-42 were deleted,and all exons of PKD1 gene were deleted(NM_001009944),and multiple ligation dependent probe amplification verified that exons 1-46 were deleted,and no downstream gene deletion was found.The overall deletion size was about 60 kb.Both of the girl's father and mother had normal phenotypes and were wild-type.Conclusions TSC2/PKD1 adjacency gene syndrome is relatively rare.It can have clinical manifestations of tuberous sclerosis/autosomal dominant polycystic kidney disease.Most of the nervous system and kidney are seriously affected,and the prognosis is poor.TSC2/PKD1 gene deletion and variation is the genetic cause of the TSC2/PKD1 adjacency gene syndrome.