不良孕产人群遗传学病因研究

Genetic etiology of adverse pregnancy and childbirth

摘要:

目的 通过染色体核型分析及临床外显子测序检测分析不良孕产人群遗传学病因，更好地指导临床工作。方法 收集2019年9月至2023年9月因不良孕产史在广东省韶关市妇幼保健院产前诊断门诊就诊的409对夫妇为研究对象。分为复发性流产组、异常胎儿组、出生缺陷儿组。269对夫妇仅行染色体检查，52对夫妇染色体正常进一步临床外显子测序，88对夫妇仅行临床外显子测序家系分析。结果 染色体检测异常人数32例，总体诊断率9.97%（32/321），三组诊断率依次为12.12%、5.26%、3.03%。外显子测序致病性（致病性/可能致病性）检测结果为38例，临床意义不明检测结果18例，总体诊断率27.14%（38/140），三组外显子测序异常检出率分别为13.64%（3/22）、27.16%（22/81）、35.14%（13/37），出生缺陷儿组临床意义不明基因变异中50%（4/8）经家系分析及重评估后改变了生育决策。结论 染色体检查在复发性流产人群临床检测效能最高，临床外显子测序在出生缺陷儿、不明原因新生儿及婴幼儿死亡人群临床检测效能最高。对基因检测意义不明结果进行家系验证及重分析，可提高临床外显子检测的阳性率，使其临床效益最大化。遗传学病因检测可指导不良孕产人群的生育决策，降低出生缺陷率。

Abstract:

Objective We analyzed the genetic etiology of the populations of adverse pregnancy and childbirth by chromosome karyotype analysis and clinical exome sequencing, for better guide clinical work.Methods From September 2019 to September 2023, 409 couples who visited the prenatal diagnosis clinic of Shaoguan Maternal and Child Health Hospital due to adverse pregnancy history were collected as research objects. They were divided into recurrent abortion group, abnormal fetal group and birth defect group. Two hundred and sixty-nine couples were performed with chromosome karyotype analysis only, 52 couples were performed with chromosome karyotype analysis and further clinical exome sequencing because of the normal chromosome result,and 88 couples were performed with trio-clinical exome sequencing only.Results There were 32 cases with abnormal chromosome, the overall detection rate was 9.97% (32/321), and the detection rates of the three groups were 12.12%, 5.26%, 3.03%, respectively. Exome sequencing detected 38 positive cases (pathogenic or likely pathogenic), also detected 18 cases of clinical uncertain significance, the overall detection rate was 27.14% (38/140), the detection rate of exome sequencing in the three groups was 13.64% (3/22), 27.16% (22/81), 35.14% (13/37), respectively. In the birth defect group, 50% (4/8) of the variants of clinical uncertain significance changed reproductive decisions after pedigree analysis and reanalysis.Conclusion The clinical efficacy of chromosome examination is the highest in recurrent abortion group, and the clinical efficacy of exome sequencing is the highest in birth defect group. To pedigree analysis and reanalysis the cases of uncertain significance can improve the positive rate of clinical exome sequencing and maximize its clinical benefit. Genetic etiology detection can guide the reproductive decision-making of adverse pregnancy and reduce the rate of birth defects.