新发NAA15基因变异导致常染色体显性遗传精神发育迟滞50型患者的临床特征及遗传学分析  

Clinical features and genetic analysis of patient with autosomal dominant mental retardation 50 caused by a de novo NAA15 gene mutation

作　　者：张李钰 王丽芳[2] 车凤玉 王国霞 李本昌 莫丽党芝 杨颖[1] ZHANG Liyu;WANG Lifang;CHE Fengyu;WANG Guoxia;LI Benchang;MOLI Dangzhi;YANG Ying(Research Institute of Pediatric Diseases of Shaanxi Province,Xi’an Children’s Hospital,Xi’an,Shaanxi 710003,China;Department of Child Care,Xi’an Children’s Hospital,Xi’an,Shaanxi 710003,China)

机构地区：[1]西安市儿童医院/陕西省儿科疾病研究所,陕西西安710003 [2]西安市儿童医院儿童保健科,陕西西安710003

出　　处：《中国优生与遗传杂志》2023年第10期2138-2142,共5页Chinese Journal of Birth Health & Heredity

基　　金：陕西省创新能力支撑计划(2019KJXX-055);陕西省自然科学基础研究计划(2023-JC-QN-0208);西安市儿童医院院级课题(2022C04)。

摘　　要：目的 对一个常染色体显性遗传精神发育迟滞50型家系患儿进行临床特征和基因变异分析,探究基因型和临床表型的相关性。方法 收集家系成员的临床资料和家族史,采用家系全外显子组测序分析患儿的致病基因,对可疑的变异位点进行家系Sanger测序验证。结果 该家系先证者临床表现为运动发育落后、语言发育落后、智力发育落后和轻微特殊面容等。测序结果显示先证者携带NAA15基因(NM_057175.5)c.1807C>T(p.Gln603Term)新发杂合变异。该变异未在文献及疾病相关数据库中报道。该变异导致NAA15蛋白第603位的谷氨酰胺突变为终止密码子,形成截短体蛋白,可能影响蛋白空间构象的稳定性从而影响蛋白功能。保守性分析结果提示上述氨基酸处于蛋白的高度保守区域。结合患儿临床表现及基因检测结果,推测先证者为NAA15基因变异导致的常染色体显性遗传精神发育迟滞50型。结论 明确了NAA15基因的无义变异为一例常染色体显性遗传精神发育迟滞50型患儿的致病原因,进一步丰富了中国该疾病的突变谱,为受累家庭的遗传咨询提供依据。Objective To analyze the clinical characteristics and gene variants of a patient affected with autosomal dominant genetic mental retardation type 50 in a pedigree and further explore the genotype-phenotype correlation for providing basis for family genetic counseling.Methods The clinical features and family history of family members were collected.The pathogenic genes were analyzed by whole exome sequencing and the suspected gene variations were verified by Sanger sequencing.Results The proband presented motor retardation,language retardation,intellectual retardation and mild facial dysmorphism.Genetic testing showed the proband carried a de novo heterozygous variant of NAA15 gene(NM_057175.5)c.1807C>T(p.Gln603Term).This variant has not been reported in the literature and disease-related databases yet.This variant could lead to deletion of amino acids at positions 603 and may cause truncation of NAA15 protein,and further influence the stability of protein spatial conformation and function.In addition,this amino acid was highly conserved in several species.According to clinical features and genetic testing results,the proband was speculated first proof of autosomal dominant intellectual disability 50 caused by NAA15 gene mutation.Conclusion This study identified the pathogenic variation of a proband with autosomal dominant mental retardation type 50 of NAA15 gene,which enriched the variation spectrum of autosomal dominant mental retardation type 50 in China,and further provided the basis for genetic counseling of affected families.

关 键 词：常染色体显性遗传精神发育迟滞50型 NAA15基因 精神发育迟缓 基因突变 

分 类 号：R749.94[医药卫生—神经病学与精神病学]