一个X连锁隐性精神发育迟滞Claes-Jensen型家系的临床特征及基因变异分析  

Clinical features and gene variant of a pedigree affected with X-linked recessive mental retardation Claes-Jensen type

作　　者：丁宁 张平平 毛莹莹[1] 冯硕[1] 高志杰[1] 陈倩[1] 张学[2] Ding Ning;Zhang Pingping;Mao Yingying;Feng Shuo;Gao Zhijie;Chen Qian;Zhang Xue(Department of Neurology,Children’s Hospital,Capital Institute of Pediatrics,Beijing 100020,China;Center for Genetic Medicine,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100005,China)

机构地区：[1]首都儿科研究所附属儿童医院神经内科,北京100020 [2]中国医学科学院基础医学研究所北京协和医学院基础学院医学遗传学系,北京100005

出　　处：《中华医学遗传学杂志》2020年第12期1352-1355,共4页Chinese Journal of Medical Genetics

基　　金：北京市科技计划项目(Z171100000417020);国家重点基础研究发展计划(973计划)(2016YFC0905100)。

摘　　要：目的对1个X连锁隐性遗传精神发育迟滞Claes-Jensen型家系进行KDM5C基因变异分析,明确其致病原因。方法采集先证者及其父母兄弟共5人外周血,进行全外显子测序,Sanger测序验证。结果测序结果提示先证者为KDM5C基因第11外显子c.1565C>T(p.Ser522Phe)半合子错义变异,Sanger测序验证其两兄长也为c.1565C>T(p.Ser522Phe)变异的半合子,母亲为c.1565C>T(p.Ser522Phe)变异杂合子,父亲未检测到KDM5C基因变异。c.1565C>T(p.Ser522Phe)变异引起患儿及其两兄长精神发育迟滞、癫痫、身材矮小、小头畸形,母亲有轻度认知障碍和学习困难。KDM5C基因第11外显子c.1565C>T(p.Ser522Phe)变异是一种未见报道过的致病变异。结论KDM5C第11外显子c.1565C>T变异是本患儿家系的致病原因。Objective To explore the genetic basis for a pedigree affected with X-linked recessive mental retardation Claes-Jensen type.Methods Genomic DNA was extracted from peripheral blood samples of the patient,his parents(phenotypically normal)and two elder brothers with similar clinical manifestations.Whole exome sequencing was carried out for the proband,and the result was verified by Sanger sequencing.Results The proband was found to harbor a hemizygous c.1565C>T missense variant in exon 11 of the KDM5C gene.The transition has resulted in replacement of serine by phenylalanine at position 522(p.Ser522Phe).Sanger sequencing showed that the patient’s two elder brothers and mother carried the same variant,which was predicted to be probably damaging by SIFT,PolyPhen2 and Mutation_Taster.The three affected brothers presented with similar clinical phenotypes characterized by mental retardation,speech delay,behavioral problem,self-limited epilepsy responsible to medication,short stature and microcephaly.The mother only had mild cognitive impairment and learning disability.The same variant was not found in their father and was unreported previously.Conclusion The c.1565C>T(p.Ser522Phe)of the KDM5C gene probably underlay the X-linked recessive mental retardation Claes-Jensen type in this pedigree.

关 键 词：KDM5C基因 基因变异 X连锁隐性精神发育迟滞综合征Claes-Jensen型 智力障碍 

分 类 号：R725.9[医药卫生—儿科]