摘要
目的对一个非综合征型先天缺牙家系进行候选致病基因测序,以寻找该家系的致病基因。方法收集首都医科大学附属北京儿童医院口腔科就诊的1例非综合征型先天缺牙患者及其家系成员的临床资料及血液标本,检测先天缺牙常见的致病基因,对寻找到的可疑突变进行生物信息学分析及表型分析。结果患者的肌节同源盒基因1(MSX1)携带一个错义突变:MSX1第2外显子发生杂合突变(c.547C>A),即核苷酸第547位C变为A,导致氨基酸第183位由谷氨酰胺(Glutamine)变为赖氨酸(Lysine),即Gln183Lys(p.Q183K)。保守性分析显示该位点在进化过程中高度保守。突变致病性预测显示该突变有很强的致病性。结论本研究在一个非综合征型先天缺牙患者中发现了MSX1基因的新突变c.547C>A,进一步证实了MSX1基因突变与非综合征型先天缺牙的关系,并扩大了MSX1基因突变谱。
Objective To search for the disease-causing gene in a family w ith non-syndromic tooth agenesis.Methods A family w ith non-syndromic tooth agenesis w as recruited from Beijing Children’s Hospital.The clinical data w ere collected and genomic DNAs w ere extracted from peripheral blood lymphocytes.The common pathogenic genes of tooth agenesis w ere detected,and the bioinformatic and phenotypic information of the suspected mutation w as analyzed.Results A de novo MSX1 missense mutation(c.547 C>A)w as identified,w hich resulted in the substitution of Gln at residue 183 for Lys(p.Q183 K);residue 105 w as located in the highly conserved region of the MSX1 protein.M utation pathogenicity predictions show ed that the mutation w as highly pathogenic.Conclusion A de novo MSX1 missense mutation is identified in a patient w ith non-syndromic tooth agenesis,w hich confirms the relationship betw een MSX1 mutation and non-syndromic tooth agenesis and extends the mutation spectrum of the MSX1 gene.
作者
丁婷婷
邹东
刘浩辰
DING Tingting;ZOU Dong;LIU Haochen(Department of Stomatology,Beijing Children's Hospital,Capital Medical University,Beijing 100045,China;Centre of Stomatology,China-Japan Friendship Hospital,Beijing 100029,China;Department of Prosthodontics,Hospital of Stomatology,Peking University,Beijing 100081,China)
出处
《山东大学学报（医学版）》
CAS
北大核心
2019年第4期97-100,105,共5页
Journal of Shandong University:Health Sciences
基金
国家自然科学基金(81600851)
