Liu Lei, Lei Tingying, Guo Fei, Ma Chunling, Zhen Li, Zhang Lina, Li Dongzhi
Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Front Genet. 2024 Aug 29;15:1448341. doi: 10.3389/fgene.2024.1448341. eCollection 2024.
The recurrent 1q21.1 microdeletion syndrome is an autosomal dominant disorder and is characterized by dysmorphic facial features, microcephaly, developmental delay, and congenital defects. However, most studies on the distal deletions in the 1q21.1 region were diagnosed postnatally. This study aimed to provide a better understanding of the ultrasound and molecular findings of fetuses with recurrent 1q21.1 microdeletions in prenatal diagnosis.
In this retrospective study, we reported 21 cases with the recurrent 1q21.1 microdeletion syndrome diagnosed at our prenatal diagnostic center from January 2016 to January 2023. The clinical data were reviewed for these cases, including the maternal demographics, indications for invasive testing, ultrasound findings, CMA results, and pregnancy outcomes.
In the study, a total of 21 cases with recurrent 1q21.1 microdeletions were diagnosed prenatally by CMA. Fifteen cases were described with ultrasound indications, and the most common findings are as follows: increased nuchal translucency (NT) (26.7%), intrauterine growth retardation (IUGR) (26.7%), congenital heart defects (CHD) (20%), and congenital anomalies of the kidney and urinary tract (CAKUT) (13.3%). All the cases with the distal 1q21.1 deletions contain the common minimal region (located between BP3 and BP4) and eight OMIM genes. Parental studies to determine the inheritance of the deletion were performed for eight cases, and half of the cases were inherited from one of the parents. Pregnancy outcomes were available for nine cases; eight (88.9%) pregnancies were determined to be terminated and one (11.1%) was full-term delivery.
To our knowledge, this is the largest study to find that fetuses with recurrent 1q21.1 microdeletions were closely associated with increased NT, CHD, IUGR, and CAKUT. In addition, ours is the first study to report that cerebral ventriculomegaly might be associated with recurrent 1q21.1 microdeletions. More comprehensive studies are needed for a better understanding of the prenatal phenotype-genotype relationship of the recurrent 1q21.1 microdeletion syndrome in future.
复发性1q21.1微缺失综合征是一种常染色体显性疾病，其特征为面部畸形、小头畸形、发育迟缓及先天性缺陷。然而，大多数关于1q21.1区域远端缺失的研究是在出生后进行诊断的。本研究旨在更好地了解产前诊断中患有复发性1q21.1微缺失的胎儿的超声及分子学表现。
在这项回顾性研究中，我们报告了2016年1月至2023年1月在我们产前诊断中心诊断出的21例复发性1q21.1微缺失综合征病例。对这些病例的临床资料进行了回顾，包括产妇人口统计学信息、侵入性检测指征、超声检查结果、染色体微阵列分析（CMA）结果及妊娠结局。
在本研究中，共有21例复发性1q21.1微缺失通过CMA在产前被诊断出来。15例有超声检查指征，最常见的表现如下：颈项透明层（NT）增厚（26.7%）、宫内生长受限（IUGR）（26.7%）、先天性心脏病（CHD）（20%）以及肾脏和泌尿系统先天性异常（CAKUT）（13.3%）。所有1q21.1远端缺失的病例均包含共同的最小区域（位于BP3和BP4之间）及8个在线人类孟德尔遗传数据库（OMIM）基因。对8例病例进行了亲代研究以确定缺失的遗传方式，其中半数病例是从父母一方遗传而来。9例有妊娠结局信息；8例（88.9%）妊娠被确定为终止妊娠，1例（11.1%）为足月分娩。
据我们所知，这是最大规模的研究，发现患有复发性1q21.1微缺失的胎儿与NT增厚、CHD、IUGR及CAKUT密切相关。此外，我们是首个报告脑室扩大可能与复发性1q21.1微缺失相关的研究。未来需要更全面的研究以更好地了解复发性1q21.1微缺失综合征的产前表型 - 基因型关系。
