KMT2C基因变异致Kleefstra综合征2型1例  

Kleefstra syndrome type 2 caused by KMT2C gene mutation:A case report

作　　者：张秋雯 郑宏[1,2] 陆相朋 卢婷婷[2] ZHANG Qiuwen;ZHENG Hong;LU Xiangpeng;LU Tingting(School of Pediatrics,He’nan University of Chinese Medicine,Zhengzhou,He’nan 450000,China;Pediatric Hospital,The First Affiliated Hospital of He’nan University of Chinese Medicine,Zhengzhou,He’nan 450000,China)

机构地区：[1]河南中医药大学儿科医学院,河南郑州450000 [2]河南中医药大学第一附属医院儿科医院,河南郑州450000

出　　处：《中国优生与遗传杂志》2024年第9期1882-1886,共5页Chinese Journal of Birth Health & Heredity

基　　金：国家自然科学基金资助项目(82274579)。

摘　　要：目的探讨1例Kleefstra综合征2型(KLEFS2)患儿的临床特征及遗传学病因。方法回顾性分析1例经基因检测最终确诊为KLEFS2患儿的临床资料并复习相关文献。结果患儿女,10岁7个月,身材矮小,边缘智力(IQ=71),注意力缺陷、多动并有语言发育迟缓史。核心家系3人外显子组测序(Trio-WES)检出患儿携带KMT2C(NM_170606.3)基因新发移码变异,即c.10825_10826delAA(p.Lys3609Glufs*5)。经Sanger验证,其父母未携带相同的变异。美国医学遗传学与基因组学学会(ACMG)判定为致病性变异(PVS1+PS2+PM2)。且该变异为首次报道。数据库共检索筛选到10篇相关英文文献,16例KLEFS2患者,结合本例中国患儿,共涉及KMT2C基因的17种变异。KLEFS2患者均有轻度至重度智力障碍、语言/运动发育迟缓和行为障碍(如自闭症谱系障碍、注意力缺陷多动症)。结论本案例丰富了KMT2C基因的变异谱。对于以智力障碍(或落后)起病的患儿,伴或不伴运动/语言发育落后、行为异常以及生长发育迟缓的患儿,建议积极行韦氏智商测试、格里菲斯发育评估量表、注意力缺陷多动障碍量表、孤独症行为评定量表评估,及早行基因检查有助于诊治。Objective Exploring the clinical features and genetic etiology of a child with Kleefstra syndrome type 2(KLEFS2).Methods The clinical data of a child with KLEFS2 who was finally diagnosed by gene detection was retrospectively analyzed,and the relevant literature was reviewed.Results The patient,a 10-year-7-month-old female with short stature,borderline intelligence(IQ=71),attention deficit hyperactivity and a history of language developmental delay.TrioWES identified a novel heterozygous pathogenic variant c.10825_10826delAA(p.K3609fs*5)in the KMT2C(NM_170606.3)gene in the patient.Sanger confirmed that her parents did not carry the same mutation.According to the guidelines of the American Society for Medical Genetics and Genomics(ACMG),it is a pathogenic variant(PVS1+PS2+PM2).And this mutation is reported for the first time.A total of 10 relevant English literature were searched and screened in the database,and 16 patients with KLEFS2 were retrieved.Together with the present Chinese child,a total of 17 variants of the KMT2C gene were involved.All reported KLEFS2 patients exhibited a core phenotype of varying degrees of intellectual disability,language/motor developmental delay,and behavioral disorders(such as autism spectrum disorders and attention-deficit/hyperactivity disorder).Conclusion This case enriches the spectrum of variants in the KMT2C gene.For children with mental retardation,with or without motor/language impairment,behavioral abnormalities,and growth retardation,it is recommended to perform Wechsler Intelligence Quotient(IQ)test,Griffiths Mental Development Scales(GMDS),attention deficit hyperactivity disorder(ADHA)test scales,and Autism Behavior Checklist(ABC),and early genetic testing can be helpful for diagnosis and treatment.

关 键 词：KMT2C基因 Kleefstra综合征2型 智力障碍 神经发育障碍 生长迟缓 

分 类 号：R748[医药卫生—神经病学与精神病学]