Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, China.
BMC Med Genomics. 2023 May 30;16(1):119. doi: 10.1186/s12920-023-01548-1.
The genetic etiology of congenital pulmonary stenosis (PS) in fetuses remains inadequately studied. We used karyotype analysis and chromosomal microarray analysis (CMA) to investigate the genetic aberrations associated with PS in human fetuses.
A retrospective analysis was performed on 84 fetuses with congenital PS in southern China. Fetal amniotic fluid and umbilical cord blood samples were obtained for chromosomal karyotype analysis and CMA.
The rate of pathogenic copy number variation (CNV) was 15.5% (13/84) after karyotyping and CMA. An abnormal karyotype was detected in five cases (6.0%, 5/84) via karyotyping, whereas pathogenic CNVs were detected in 13 cases (15.5%, 13/84) via CMA. In addition to the five abnormal karyotypes detected using karyotype analysis, eight additional chromosomal microduplications and microdeletions were detected using CMA, comprising three cases of 22q11.21 microdeletion; two cases of 16p11.2 microdeletion; one case of simultaneous 18q23 microdeletion and 22q13.33 microduplication; one case of 15q24.1q24.2 microdeletion; and one case of 1q21.1q21.2 microduplication. The rate of pathogenic CNV occurrence was 11.5% in fetuses with isolated PS and 17.2% in fetuses with PS combined with other ultrasound abnormalities. This difference between the two experimental groups was statistically significant. Among 84 fetuses with PS, 39 pregnancies were terminated, and five were lost to follow-up.
CMA was not only conducive to detect PS-related pathogenic genomic abnormalities but also to accurately evaluate fetal prognosis in genetic counseling. The early detection of PS and genomic abnormalities will exerta positive impact on fetal intervention and the related prognosis of PS in perinatal infants.
胎儿先天性肺动脉瓣狭窄（PS）的遗传病因仍研究不足。我们使用核型分析和染色体微阵列分析（CMA）来研究与人类胎儿 PS 相关的遗传异常。
对中国南方 84 例先天性 PS 胎儿进行回顾性分析。获取胎儿羊水和脐血样本进行染色体核型分析和 CMA。
核型分析和 CMA 后致病性拷贝数变异（CNV）的检出率为 15.5%（13/84）。核型分析检出 5 例（6.0%，5/84）异常核型，CMA 检出 13 例（15.5%，13/84）致病性 CNV。除核型分析检出的 5 种异常核型外，CMA 还检出 8 种额外的染色体微重复和微缺失，包括 3 例 22q11.21 微缺失；2 例 16p11.2 微缺失；1 例同时 18q23 微缺失和 22q13.33 微重复；1 例 15q24.1q24.2 微缺失；1 例 1q21.1q21.2 微重复。单纯 PS 胎儿的致病性 CNV 发生率为 11.5%，PS 合并其他超声异常胎儿的致病性 CNV 发生率为 17.2%。两组间差异有统计学意义。84 例 PS 胎儿中，39 例妊娠终止，5 例失访。
CMA 不仅有利于检测 PS 相关的致病性基因组异常，还有助于在遗传咨询中准确评估胎儿预后。早期检测 PS 和基因组异常将对胎儿干预和围产儿 PS 的相关预后产生积极影响。
