摘要目的:分析胎儿Zellweger谱系障碍（Zellweger spectrum disorders，ZSD）的产前表型和基因型特点。方法:回顾性分析2020年6月至2021年12月在郑州大学第三附属医院（河南省妇幼保健院）产前诊断中心行家系基因检测诊断明确的3例ZSD胎儿及其父母的临床资料。结合既往文献，总结产前表型和基因型特点。对数据资料采用描述性统计分析。结果:3例胎儿的母亲均为初产，年龄分别为32、29和33岁，首次发现胎儿异常孕周分别为23周 +2、24周和33周 +3。例1胎儿仅表现为颈后皮肤增厚，例2～3表现为大脑结构异常。3例染色体微阵列分析均未检测到致病或可能致病的拷贝数变异，但例1胎儿分别在6q13q15和7q21.13q22.1检测到临床意义未明的杂合性缺失。3例胎儿均检测出 PEX1致病性变异，变异均来自父母。例3发现的新发杂合变异c.1246_1247del未检索到国内报道。3个家系均选择引产终止妊娠。家系2孕妇于半年后自然妊娠，孕早期发现 PEX1基因c.892_895dup（p.N299Ifs*2）致病性杂合变异，为 PEX1基因致病性杂合变异携带者。该孕妇继续妊娠至足月分娩，随访新生儿情况良好。其余2个家系未再妊娠。 结论:ZSD的变异谱可能以 PEX1基因变异为主。当产前检查时发现胎儿颅面畸形、脑结构异常、颈后皮肤层增厚、肝肾高回声等异常表现时应加强警惕，完善基因检测，以减少出生缺陷。

abstractsObjective:To analyze the clinical phenotypes and genotypes of fetal Zellweger spectrum disorders (ZSD).Methods:A retrospective analysis was conducted on the clinical data of three fetuses diagnosed with ZSD and their parents, who underwent family genetic testing at the Prenatal Diagnosis Center of the Third Affiliated Hospital of Zhengzhou University (Maternal and Child Health Hospital of Henan Province) from June 2020 to December 2021. The prenatal phenotypic and genotypic characteristics were summarized in combination with previous literature. Descriptive statistical analysis was used for the data.Results:The mothers of the three fetuses were all primiparous, aged 32, 29, and 33 years, respectively. The gestational weeks at the first detection of fetal abnormalities were 23 weeks and 2 days, 24 weeks, and 33 weeks and 3 days, respectively. Case 1 only showed increased nuchal translucency, while Case 2 and 3 showed brain structural abnormalities. Chromosomal microarray analysis of the three cases did not detect any pathogenic or potentially pathogenic copy number variations. However, heterozygous deletions of unknown significance at 6q13q15 and 7q21.13q22.1 were detected in Case 1. All three fetuses were found to have pathogenic PEX1 variants, which were inherited from their parents. A novel heterozygous variant c.1 246_1247del detected in Case 3 was not previously reported in China. All three families chose to terminate the pregnancies. The mother in family 2 conceived naturally six months later, and an early pregnancy test revealed a pathogenic heterozygous variant c.892_895dup (p.N299Ifs*2) in the PEX1 gene, leading to a diagnosis of being a carrier of the pathogenic PEX1 variant. She continued the pregnancy to full term, and the newborn was followed up with good health. The remaining two families did not have any further pregnancies. Conclusions:PEX1 gene variants may predominantly characterize the mutation spectrum of ZSD. When prenatal examinations reveal fetal craniofacial malformations, brain structural abnormalities, increased nuchal translucency, or high echogenicity of the liver and kidneys, heightened vigilance and comprehensive genetic testing are warranted to reduce birth defects.