摘要
目的分析一个Usher综合征I型家系的MYO7A基因变异情况,并分析其临床表型与基因型关系。方法对先证者及家系成员进行病史采集、全身体格检查。收集先证者及家系成员的外周血,提取基因组DNA,使用高通量测序技术对先证者、其弟弟及父母进行基因检测,应用Sanger测序对疑似致病变异进行家系验证。结果先证者临床诊断为极重度感音神经性耳聋和视网膜色素变性,其弟弟为耳聋患儿,无视网膜病变,父母及姐妹表型正常。高通量测序及Sanger测序结果显示,先证者携带MYO7A c.3631-1G>C和c.6049C>T(p.Q2017*)复合杂合变异,其弟弟携带相同的变异位点。先证者父亲、姐姐及妹妹均携带c.3631-1G>C杂合剪接变异,母亲携带c.6049C>T杂合无义变异。氨基酸功能影响预测提示,两种变异均为致病性变异。结论发现了一个新的MYO7A基因变异c.3631-1G>C,丰富了MYO7A基因变异谱,为Usher综合征的遗传咨询提供依据。
Objective To analyze the mutation of MYO7A gene in a family with Usher syndrome type I,and analyze the relationship between its clinical phenotype and genotype.Methods Medical history collection and full physical examination were performed on the proband and family members.With genomic DNA extracted from peripheral blood samples,potential variants in the proband,her brother and parents were detected by next generation sequencing.Suspected variants were validated by Sanger sequencing.Results The proband was clinically diagnosed with extremely severe sensorineural hearing loss and retinitis pigmentosa.Her younger brother was a deaf child without retinopathy,and her parents and sisters had normal phenotypes.Next generation sequencing and Sanger sequencing revealed that the proband has carried compound heterozygous variants of the MYO7A gene,namely c.3631-1G>C and c.6049C>T(p.Q2017*),and her brother carried the same variant.Her father,elder sister and younger sister carry the c.3631-1G>C heterozygous splicing variant,and her mother carries the c.6049C>T heterozygous nonsense variant.The predicted effects of amino acid function suggest that both variants are pathogenic.Conclusion A novel MYO7A gene mutation c.3631-1G>C was found,which enriched the MYO7A gene mutation spectrum and provided a basis for genetic counseling of Usher syndrome.
作者
严提珍
黄钧
袁德健
唐向荣
韦笑宝
罗世强
无
YAN Ti-zhen;HUANG Jun;YUAN De-jian;TANG Xiong-rong;WEI Xiao-bao;LUO Shi-qiang
出处
《中国听力语言康复科学杂志》
2021年第3期183-186,共4页
Chinese Scientific Journal of Hearing and Speech Rehabilitation
基金
广西自然科学资金(2020GXNSFAA297059)
广西壮族自治区卫生健康委员会科研课题(Z20200018)
柳州市科技创新能力与条件建设项目(2018AF10501)。
