PDF(Pubmed)
Abstract：
OBJECTIVE: To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale, multicenter carrier screening.
METHODS: This study was conducted among a total of 33 104 participants (16 610 females) from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.
RESULTS: The overall combined carrier frequency was 55.58% for 197 autosomal genes and 1.84% for 26 X-linked genes in these participants.Among the 16 669 families, 874 at-risk couples (5.24%) were identified.Specifically, 584 couples (3.50%) were at risk for autosomal genes, 306(1.84%) for X-linked genes, and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A, 393 couples), HBA1/HBA2(α-thalassemia, 36 couples), PAH (phenylketonuria, 14 couples), and SMN1(spinal muscular atrophy, 14 couples).The most frequently detected X-linked at-risk genes were G6PD (G6PD deficiency, 236 couples), DMD (Duchenne muscular dystrophy, 23 couples), and FMR1(fragile X syndrome, 17 couples).After excluding GJB2 c.109G>A, the detection rate of at-risk couples was 3.91%(651/16 669), which was lowered to 1.72%(287/16 669) after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95% of at-risk couples, while screening for the top 54 genes further increased the detection rate to over 99%.
CONCLUSIONS: This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing, genetic counseling for specific genes or gene variants can be challenging, and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.
METHODS: This study was conducted among a total of 33 104 participants (16 610 females) from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.
RESULTS: The overall combined carrier frequency was 55.58% for 197 autosomal genes and 1.84% for 26 X-linked genes in these participants.Among the 16 669 families, 874 at-risk couples (5.24%) were identified.Specifically, 584 couples (3.50%) were at risk for autosomal genes, 306(1.84%) for X-linked genes, and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A, 393 couples), HBA1/HBA2(α-thalassemia, 36 couples), PAH (phenylketonuria, 14 couples), and SMN1(spinal muscular atrophy, 14 couples).The most frequently detected X-linked at-risk genes were G6PD (G6PD deficiency, 236 couples), DMD (Duchenne muscular dystrophy, 23 couples), and FMR1(fragile X syndrome, 17 couples).After excluding GJB2 c.109G>A, the detection rate of at-risk couples was 3.91%(651/16 669), which was lowered to 1.72%(287/16 669) after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95% of at-risk couples, while screening for the top 54 genes further increased the detection rate to over 99%.
CONCLUSIONS: This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing, genetic counseling for specific genes or gene variants can be challenging, and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.
摘要：
目的:通过大规模研究中国人群单基因病的流行病学特征和突变谱,多中心载体筛选。
方法：这项研究是在来自中国12个临床中心的33104名参与者（16610名女性）中进行的。使用高通量测序和不同的PCR方法分析了223个基因的载体状态。
结果：在这些参与者中，197个常染色体基因的总体组合携带者频率为55.58％，26个X连锁基因的总体组合携带者频率为1.84％。在16669个家庭中，确定了874对有风险的夫妇（5.24％）。具体来说,584对夫妇（3.50％）有常染色体基因的风险，306（1.84%）的X连锁基因，常染色体和X连锁基因均为16。最常见的常染色体风险基因包括GJB2（常染色体隐性耳聋1A型，393对夫妇），HBA1/HBA2（α-地中海贫血，36对夫妇），PAH（苯丙酮尿症，14对夫妇），和SMN1（脊髓性肌萎缩症，14对夫妇）。最常见的X连锁风险基因是G6PD（G6PD缺乏症，236对夫妇)，DMD（杜氏肌营养不良症，23对夫妇），和FMR1（脆性X综合征，17对夫妇）。排除GJB2c.109G>A后，高危夫妇的检出率为3.91%(651/16669)，在进一步排除G6PD后，降至1.72%(287/16669)。严重单基因出生缺陷的理论发生率约为4.35‰（72.5/16669）。筛选高危夫妇中最常见的22种基因，可以检测到超过95％的高危夫妇，而筛选前54个基因的检出率进一步提高到99%以上。
结论：这项研究揭示了中国人群中223种单基因遗传病的携带者频率，并为针对中国人群的携带者筛查策略开发和小组设计提供了证据。在载体测试中，针对特定基因或基因变异的遗传咨询可能具有挑战性，夫妇需要在测试前了解这些困难，并提供不筛查这些基因或基因变异的选择。
方法：这项研究是在来自中国12个临床中心的33104名参与者（16610名女性）中进行的。使用高通量测序和不同的PCR方法分析了223个基因的载体状态。
结果：在这些参与者中，197个常染色体基因的总体组合携带者频率为55.58％，26个X连锁基因的总体组合携带者频率为1.84％。在16669个家庭中，确定了874对有风险的夫妇（5.24％）。具体来说,584对夫妇（3.50％）有常染色体基因的风险，306（1.84%）的X连锁基因，常染色体和X连锁基因均为16。最常见的常染色体风险基因包括GJB2（常染色体隐性耳聋1A型，393对夫妇），HBA1/HBA2（α-地中海贫血，36对夫妇），PAH（苯丙酮尿症，14对夫妇），和SMN1（脊髓性肌萎缩症，14对夫妇）。最常见的X连锁风险基因是G6PD（G6PD缺乏症，236对夫妇)，DMD（杜氏肌营养不良症，23对夫妇），和FMR1（脆性X综合征，17对夫妇）。排除GJB2c.109G>A后，高危夫妇的检出率为3.91%(651/16669)，在进一步排除G6PD后，降至1.72%(287/16669)。严重单基因出生缺陷的理论发生率约为4.35‰（72.5/16669）。筛选高危夫妇中最常见的22种基因，可以检测到超过95％的高危夫妇，而筛选前54个基因的检出率进一步提高到99%以上。
结论：这项研究揭示了中国人群中223种单基因遗传病的携带者频率，并为针对中国人群的携带者筛查策略开发和小组设计提供了证据。在载体测试中，针对特定基因或基因变异的遗传咨询可能具有挑战性，夫妇需要在测试前了解这些困难，并提供不筛查这些基因或基因变异的选择。
