中国人群腺苷脱氨酶2缺乏症致病基因携带者筛查

Screening for carriers of pathogenic gene for deficiency of adenosine deaminase 2 in China

目的分析中国人群腺苷脱氨酶2缺乏症(deficiency of adenosine deaminase 2,DADA2)致病基因频率,为有效开展中国人群DADA2的防控和干预工作提供依据。方法回顾性分析2015年1月至2021年1月于北京智因东方转化医学研究中心有限公司进行全外显子组测序的11.1万例原始数据,对ADA2基因致病和可能致病性突变进行携带者筛查,分析ADA2基因杂合突变的类型和等位基因频率。结果发现29种ADA2基因致病和可能致病性杂合突变,其中6种[c.730G>T(p.E244X)、c.1049_c.1061 delAGCTGCCTTACTT(p.K350Tfs*14)、c.940A>T(p.K314X)、c.1239+2(IVS8)T>C、c.1240-1(IVS8)G>A、c.1087C>T(p.Q363X)]既往未见报道,等位基因累计频率为0.58%。人群基因频率最高的为p.F355L(0.5%),其次为p.Y453C(0.014%)和p.P193L(0.013%),其他26种位点均小于0.01%,为罕见突变位点。结论通过筛查丰富了ADA2基因突变谱,明确了中国地区人群的ADA2基因突变的携带率约1/171,推测中国人群的DADA2患病率约1/116964。

Objective To analyze frequency of pathogenic gene for deficiency of adenosine deaminase 2(DADA2)in China,so as to provide basis for effective prevention and intervention of DADA2.Methods The original data of 111000 subjects of whole exome sequencing performed in Chigene(Beijing)Translational Medical Research Center Co.Ltd.from January 2015 to January 2021 were retrospectively analyzed.The types of variants and allele frequency of ADA2 gene were analyzed.Results 29 heterozygous variants of ADA2 gene were found.There were 6 ADA2 variants unreported previously,including c.730G>T(p.E244X),c.1049_c.1061delAGCTGCCTTACTT(p.K350Tfs*14),c.940A>T(p.K314X),c.1239+2(IVS8)T>C,c.1240-1(IVS8)G>A,c.1087C>T(p.Q363X),and the cumulative allele frequency of ADA2 was 0.58%.The highest allele frequency of p.F355L was 0.5%,followed by p.Y453C(0.014%)and p.P193L(0.013%).Other 26 variant sites were less than 0.01%,indicating rare variant.Conclusion It enriched the variational spectrum of ADA2 gene by the screening.The carrier frequency of ADA2 gene in China population was about 1 in 171 individuals,corresponding to an expected DADA2 disease prevalence of 1 in 116964 individuals.