Objective: To detect the incidence and analyze the clinical significance of regions of homozygosity (ROH) through the single nucleotide polymorphism array (SNP array). Methods: The SNP array detection results of 5 116 pregnant women in the Third Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2020 were retrospectively analyzed. The pregnant women with ROH (5 Mb as the threshold) were followed up to analyze the relationship between ROH and abnormal fetal phenotype. Whole exon sequencing was performed in 4 cases of consanguineous marriage to detect potential recessive causative genes in the ROH region. Results: (1) A total of 39 cases of ROH were detected, with a positive rate of 0.76% (39/5 116). Among them, 25 cases (64%, 25/39) were detected only on single chromosome, and chromosome 11 had the highest detection rate, suggesting the risk of uniparental disomy; fourteen cases (36%,14/39) were detected on multiple chromosomes, most commonly on chromosomes 11, 1, 3, 4 and 8. (2) The number of cases and detection rate of ROH detected by different prenatal diagnosis indicators were as follows: 12 cases (1.78%, 12/676) in pregnant women with abnormal non-invasive prenatal testing result, 12 cases (0.37%, 12/3 284) in pregnant women with ultrasound abnormality, 4 cases (4/4) in pregnant women with consanguineous marriage, 3 cases (0.92%, 3/326) in pregnant women with previous adverse pregnancy, 2 cases (1.15%, 2/174) in pregnant women with high risk of serology in screening, 2 cases (4.00%, 2/50) in pregnant women with abnormal fetal chromosomal karyotype, 2 cases (0.79%, 2/253) in pregnant women with advanced maternal age, 1 case (0.56%, 1/178) in pregnant women with related parental genetic factors and 1 case (0.58%, 1/171) in pregnant women with the other factors. (3) The follow-up results of 39 cases of prenatal ROH showed that there were 16 cases of term birth, 15 cases of termination of pregnancy, 2 cases of preterm births, 1 case of fetal death and 5 cases lost to follow-up. Conclusions: Chromosomal ROH phenomenon is not rare. By analyzing the detection rate of ROH in prenatal diagnosis, combined with the results of fetal phenotype and postpartum follow-up, the clinical characteristics of ROH are discussed, so as to better understand the relationship between ROH and its phenotype.
目的： 探讨产前诊断中应用单核苷酸多态性微阵列（SNP array）技术检测染色体纯合区域（ROH）的检出率并分析其临床意义。 方法： 回顾性分析2016年1月至2020年12月广州医科大学附属第三医院5 116例孕妇的SNP array检测结果，对检出ROH（以5 Mb为阈值）的孕妇进行随访，分析ROH与胎儿异常表型之间的关系。进一步对4例近亲婚配孕妇行全外显子测序，检测ROH区域潜在的致病性变异位点。 结果： （1）共检出ROH 39例，检出率为0.76%（39/5 116），其中25例（64%，25/39）仅在单条染色体上检出，以11号染色体检出率最高，提示单亲二倍体的风险；14例（36%，14/39）在多条染色体上检出，常见于11、1、3、4、8号染色体。（2）不同产前诊断指征的ROH检出例数及检出率分别为：无创性产前基因检测筛查高风险孕妇中检出12例（1.78%，12/676）、超声检查结果异常孕妇中检出12例（0.37%，12/3 284）、近亲婚配孕妇中检出4例（4/4）、既往不良妊娠史孕妇中检出3例（0.92%，3/326）、产前血清学筛查高风险孕妇中检出2例（1.15%，2/174）、胎儿染色体核型异常孕妇中检出2例（4.00%，2/50）、高龄妊娠孕妇中检出2例（0.79%，2/253）、遗传因素孕妇中检出1例（0.56%，1/178）、其他孕妇中检出1例（0.58%，1/171）。（3）39例产前检出ROH孕妇的随访结果显示，足月产16例，人工终止妊娠15例，早产存活2例，胎儿足月胎死宫内1例，失访5例。 结论： 染色体ROH现象并不罕见，通过分析产前诊断中ROH的检出率，结合胎儿表型及产后随访结果，探讨ROH的临床特点，有利于更好地了解ROH与其表型之间的关系。.