CNTNAP2基因变异导致Pitt-Hopkins样综合征1型1例  

CNTNAP2 gene variants causing a child with Pitt-Hopkins-like syndrome 1

作　　者：丛妍 王浩 王栋 吴轲 CONG Yan;WANG Hao;WANG Dong;WU Ke(Rehabilitation Department,Yiwu Maternity and Children Hospital,Yiwu,Zhejiang 322000,China;Laboratory ofPrenatal Diagnosis Center,Quzhou Maternity and Child Health Care Hospital,Quzhou,Zhejiang 324000,China)

机构地区：[1]义乌市妇幼保健院康复科,浙江义乌322000 [2]衢州市妇幼保健院产前诊断实验室,浙江衢州324000

出　　处：《中国优生与遗传杂志》2024年第2期380-384,共5页Chinese Journal of Birth Health & Heredity

基　　金：浙江省金华市科研计划项目(22-4-348)。

摘　　要：目的 分析CNTNAP2基因变异引起婴幼儿期癫痫发作、精神运动发育迟缓。方法 患儿,女,5岁4月龄,因“运动、语言、认知落后”来我院康复科就诊。患儿主要表现为精神运动发育迟缓、癫痫,共济失调,现有孤独症倾向。患儿行染色体微阵列检测(CMA)和家系全外显子组测序分析(trio-WES)。结果 CMA结果未见异常。WES发现2个复合杂合致病变异CNTNAP2(NM_014141.6):c.451C>T(p.Q151^(*)),来源于母亲;c.3588_3591delGACA(N1198Pfs^(*)21),来源于父亲;变异与Pitt-Hopkins样综合征1型(PTHSL1)相关。Sanger测序验证结果与WES结果一致。这2个变异可能影响CNTNAP2蛋白的盘状结构域(discoidin domain,又称F5/8 C型结构域)和层粘连蛋白G样结构域(laminin G-like 4)功能异常,从而引起患儿癫痫发作和精神运动发育迟缓。结论 CNTNAP2基因纯合变异或复合杂合变异导致的主要临床表现为认知障碍、癫痫和行为异常。国内尚未见PTHSL1报道,本研究报道2个新的CNTNAP2基因致病变异,有助于提高临床医师对此疾病的临床诊断和遗传咨询能力。Objective To analyze the phenotypes of a child with epilepsy and psychomotor development delay who carried CNTNAP2 gene variants.Methods The child,aged 5 years and 4 months,was admitted to our hospital's rehabilitation department due to delay in motor,language and cognition.The patient primarily presented with psychomotor retardation,epilepsy,ataxia and tendencies towards autism.Chromosomal microarray analysis(CMA) and trio-whole-exome sequencing(trio-WES) were performed on the child.Results The CMA resuls showed no abnormalities.Trio-WES identified two pathogenic compound heterozygous CNTNAP2(NM_014141.6) variants [c.451C>T(p.Q151~*) derived from her mother,c.3588_3591delGACA(N1198Pfs~*21) derived from her father].These two CNTNAP2 variants are associated with Pitt-Hopkins-like syndrome 1.Sanger sequencing confirmed the findings of trio-WES.These two variants may damage the discoidin domain(also known as F5/8 C-domain) and laminin G-like 4 domain of CNTNAP2 protein,which may lead to seizures and psychomotor retardation.Conclusion Homozygous or compound heterozygous CNTNAP2 gene variants result in severe cognitive impairment,epilepsy,and behavioral abnormalities as main clinical manifestations.PTHSL1 has not been reported in China before this study,therefore this study reports two novel pathogenic CNTNAP2 gene variants that can assist clinicians in improving their ability for clinical diagnosis and genetic counseling.

关 键 词：癫痫 Pitt-Hopkins样综合征1型 CNTNAP2基因 

分 类 号：R725.9[医药卫生—儿科]