Yue Fagui, Yang Xiao, Jiang Yuting, Li Shibo, Liu Ruizhi, Zhang Hongguo
Center for Reproductive Medicine and Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun, China.
Jilin Engineering Research Center for Reproductive Medicine and Genetics, Jilin University, Changchun, China.
Front Med (Lausanne). 2023 Aug 24;10:1207891. doi: 10.3389/fmed.2023.1207891. eCollection 2023.
Chromosomal 1q21.1 deletions and duplications are genomic disorders that are usually diagnosed postnatally. However, the genotype-phenotype correlations of 1q21.1 copy number variants (CNVs) during the prenatal period are still not clear. This study aimed to provide a systematic summary of prenatal phenotypes for such genomic disorders.
In total, 26 prenatal amniotic fluid samples diagnosed with 1q21.1 microdeletions/microduplications were obtained from pregnant women who opted for invasive prenatal testing. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed for all cases simultaneously. The pregnancy outcomes and health conditions after birth in all cases were followed up. Meanwhile, prenatal cases with 1q21.1 microdeletions or microduplications in the literature were retrospectively collected.
In total, 11 pregnancies (11/8,252, 0.13%) with 1q21.1 microdeletions and 15 (15/8,252, 0.18%) with 1q21.1 microduplications were identified. Among these 1q21.1 CNVs, 4 cases covered the thrombocytopenia-absent radius (TAR) region, 16 cases covered the 1q21.1 recurrent microdeletion/microduplication region, and 6 cases covered all regions mentioned above. The prenatal abnormal ultrasound findings were recorded in four participants with 1q21.1 deletions and seven participants with 1q21.1 duplications. Finally, three cases with 1q21.1 deletions and five with 1q21.1 duplications terminated their pregnancies.
In the prenatal setting, 1q21.1 microdeletions were associated with increased nuchal translucency (NT), anomalies of the urinary system, and cardiovascular abnormalities, while 1q21.1 microduplications were correlated with cardiovascular malformations, nasal bone dysplasia, and increased NT. In addition, cerebral ventriculomegaly might be correlated with 1q21.1 microduplications. Considering the variable expressivity and incomplete penetrance of 1q21.1 CNVs, long-term follow-up after birth should be carried out in these cases.
1q21.1染色体缺失和重复是通常在出生后才被诊断出的基因组疾病。然而，孕期1q21.1拷贝数变异（CNV）的基因型-表型相关性仍不明确。本研究旨在系统总结此类基因组疾病的产前表型。
从选择侵入性产前检测的孕妇中总共获取了26例诊断为1q21.1微缺失/微重复的产前羊水样本。对所有病例同时进行核型分析和染色体微阵列分析（CMA）。对所有病例的妊娠结局和出生后的健康状况进行随访。同时，回顾性收集文献中1q21.1微缺失或微重复的产前病例。
总共鉴定出11例（11/8252，0.13%）1q21.1微缺失妊娠和15例（15/8252，0.18%）1q21.1微重复妊娠。在这些1q21.1 CNV中，4例覆盖血小板减少-桡骨缺失（TAR）区域，16例覆盖1q21.1反复微缺失/微重复区域，6例覆盖上述所有区域。4例1q21.1缺失参与者和7例1q21.1重复参与者记录了产前异常超声检查结果。最后，3例1q21.1缺失病例和5例1q21.1重复病例终止了妊娠。
在产前情况下，1q21.1微缺失与颈项透明层（NT）增厚、泌尿系统异常和心血管异常有关，而1q21.1微重复与心血管畸形、鼻骨发育不良和NT增厚有关。此外，脑室扩大可能与1q21.1微重复有关。考虑到1q21.1 CNV的可变表达性和不完全外显率，应对这些病例进行出生后的长期随访。
