Treacher Collins综合征1例基因突变分析  

Gene mutation analysis of a patient with Treacher Collins syndrome

作　　者：王小雨 沈露 王凤琦 张铷 刘世国[1] WANG Xiaoyu;SHEN Lu;WANG Fengqi;ZHANG Ru;LIU Shiguo(Department of Medical Genetics,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院医学遗传科,山东青岛266003

出　　处：《青岛大学学报（医学版）》2024年第1期43-46,共4页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金面上项目(30971586)。

摘　　要：目的分析1例Treacher Collins综合征(TCS)病人的遗传学改变,探讨该病例基因型-表型的关系。方法提取先证者及其父母外周静脉血全基因组DNA和RNA,利用全外显子测序(WES)对先证者进行突变筛查,采用Sanger测序在先证者及其父母中进行验证。结果先证者符合TCS的典型临床症状。基因检测分析结果显示,该病例TCOF1基因第18外显子最后一个碱基发生c.3183G>A(p.Q1061=)突变,但表型正常的父母不存在此突变,因此该突变是一个de-novo遗传的突变。RNA验证显示,先证者与健康人的TCOF1 mRNA水平存在显著差异(t=-27.488,P<0.01)。结论TCOF1基因c.3183G>A突变很可能是TCS的致病突变位点。本研究结果有助于了解和完善中国TCS病人的遗传学基础。Objective To analyze the genetic changes of a patient with Treacher Collins syndrome(TCS)and explore the genotype-phenotype relationship.Methods The whole-genomic DNA and RNA were extracted from the peripheral venous blood of the proband and her parents.Whole-exome sequencing was used to detect the gene mutations of the proband,followed by verification with Sanger sequencing in the proband and her parents.Results The proband met the typical clinical symptoms of TCS.A mutation of c.3183G>A(p.Q1061=)was detected at the last base of exon 18 of the TCOF1 gene in this case,but not in her parents with a normal phenotype,indicating a de-novo genetic mutation.The RNA validation analysis showed a significant diffe-rence(t=-27.488,P<0.01)in the TCOF1 mRNA level between the proband and healthy controls.Conclusion The c.3183-G>A mutation of the TCOF1 gene is the probable pathogenic mutation of TCS.This study is helpful for understanding and improving the genetic basis of Chinese patients with TCS.

关 键 词：Treacher Collins综合征 全外显子组测序 基因 TCOF1 基因突变 

分 类 号：R394[医药卫生—医学遗传学]