摘要目的 探究中国人群中高频携带的基因突变及相对应的疾病,为确定遗传病携带者筛查疾病范围做参考.方法 选取从2017年7月-2018年7月期间在北京诺禾致源科技股份有限公司做过全外显子测序的健康且无亲缘关系人群200例,分析133种单基因隐性遗传病相关的197个基因,筛选出变异位点,按照美国医学遗传学与基因组学学会(ACMG)指南对其进行解读,得出携带的变异位点致病性与否的结论,并在总体样本中做统计分析.结果 甲状腺激素合成及功能障碍、非综合征耳聋和视网膜色素变性这3种疾病相关的基因突变在中国人群中不仅携带率高,而且突变位点种类多.鉴定出78个突变位点,其中有4个(MYO15A c.5919G＞A、TYR c.929_ 930insC、DUOX2 c.3329G＞A、ABCB11 c.2842C＞T)经过分析解读,被判断为致病位点,在被测样本中为杂合突变,是相应的携带者.并且,还检测到9个从未报道过的新的突变类型,这些突变为临床意义未明位点.结论 在200例中国人群中筛选出了高频携带的基因突变,初步确定甲状腺激素合成及功能障碍、非综合征耳聋和视网膜色素变性等疾病可作为中国人群携带者筛查的重点对象.

abstractsObjective To investigate the variants in the high frequency associated with corresponding diseases in Chinese population,and to identify disease coverage for carriers screening in China.Methods A total of 200 normal and unrelated Chinese samples who accepted whole exome sequencing in Novogene Co.Ltd from July 2017 to July 2018 were subjected to screen for the genes associated with 133 single-gene recessive diseases.Then the variants were identified and interpreted by American College of Medical Genetics and Genomics (ACMG) guidelines,which were analyzed as pathogenic or benign.A total variants detected in all of the sample were counted.Results It was found that the variants related to thyroid dyshormonogenesis,non-syndromic deafness and retinitis pigmentosa were not only highly carried in the Chinese population,but also had many mutation types.In addition,a total of 78 variants were identified.And 4 of them (MYO15A c.5919G＞A,TYR c.929_930insC,DUOX2 c.3329G＞A,ABCB 11 c.2842C＞T) were analyzed as pathogenic mutations,which were heterozygous and carried by four individuals.Moreover,9 novel mutations were found that have never been reported,and these mutations were considered as uncertain significance.Conclusion High-frequency genetic mutations with the corresponding diseases were identified in 200 Chinese populations.Preliminary conclusions indicate that thyroid dyshormonogenesis,non-syndromie deafness and retinitis pigmentosa can be the focus for carriers screening in China.