产前诊断中额外标记染色体的遗传学分析

Genetic analysis of extra marker chromosomes in prenatal diagnosis

摘要

目的 探讨产前诊断标本中额外标记染色体(SMC)的检出率、遗传物质及来源、妊娠结局等,为产前诊断工作中SMC的遗传咨询提供参考。方法 回顾性分析2015年1月至2022年6月于贵阳市妇幼保健院优生遗传科行产前诊断的13640例标本,统计其中经细胞和分子遗传学检测出SMC病例的产前诊断指征及随访妊娠结局,分析SMC遗传来源及遗传学效应。结果 在13640例产前诊断样本中,共检出16例SMC,总检出率为1.17‰,其中9例为嵌合体,占56.25%.对13例孕妇进一步行染色体微阵列分析,其中发现有不同染色体片段的重复与缺失11例,结果未见异常2例;对11例行亲本验证,其中新发变异8例.成功随访15例妊娠结局,其中终止妊娠10例,孕27周早产后夭折1例,继续妊娠至生产4例,后期随访语言发育迟缓1例,运动发育迟缓1例,其余良好。结论 SMC引起的临床后果差异很大,需要结合细胞和分子遗传学检测技术确定SMC的遗传物质及嵌合程度,以明确其致病性及可能引起的临床表型,为产前诊断提供准确有效地遗传咨询.

Abstract

Objective The purpose of this study is to investigate the detection rate of supernumerary marker chromosomes (SMC) in prenatal diagnostic specimens, as well as their genetic material and origin, and the pregnancy outcome. The results will provide a reference for genetic counseling of SMC in prenatal diagnostic work. Methods A retrospective analysis was conducted on 13640 prenatal diagnostic specimens collected at the Department of Eugenics and Genetics, Guiyang Maternal and Child Health Hospital from January 2015 to June 2022. The prenatal diagnostic indications and follow-up pregnancy outcomes of SMC cases detected through cytogenetic and molecular genetic testing were statistically analyzed, along with the genetic origins and genetic effects of SMCs. Results Among the 13640 prenatal diagnostic samples, 16 cases of SMCs were detected, with a total detection rate of 1.17‰. Among these, 9 cases (56.25%) were mosaics. Chromosomal microarray analysis (CMA) was performed on 13 pregnant women, revealing duplications and deletions of various chromosomal segments in 11 cases, while no abnormalities were found in 2 cases. Parental verification was conducted for 11 cases, identifying 8 cases as de novo mutations. Follow-up data on 15 pregnancy outcomes showed 10 cases of pregnancy termination, 1 case of preterm birth at 27 weeks with neonatal death, and 4 cases of continued pregnancies resulting in live births. Among the live births, delayed language development was observed in 1 case, delayed motor development in another, while the remaining cases showed favorable outcomes. Conclusion The clinical outcomes caused by SMCs vary greatly. It is necessary to utilize cytogenetic and molecular genetic testing techniques to determine the genetic material and mosaicism levels of SMCs, in order to clarify their pathogenicity and potential clinical phenotypes, providing accurate and effective genetic counseling for prenatal diagnosis.

关键词

标记染色体 / 染色体微阵列分析 / 产前诊断 / 遗传咨询

Key words

marker chromosome / chromosome microarray analysis / prenatal diagnosis / genetic counseling

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基金资助

贵阳市卫生健康局科学计划项目([2021]32)

贵州省高层次人才计划(GCC[2022]019)