【摘要】 目的 探讨罕见嵌合体合并单基因变异的产前诊断策略、分子形成机制及临床预后，为遗传咨询与管理提供循证依据。方法 2025年9月就诊于湛江市妇幼保健院的1例不良孕产史孕妇，联合超声检查、家系短串联重复序列（short tandem repeats,STR）比对、母源污染鉴定、染色体核型分析、染色体微阵列分析（chromosomal microarray analysis,CMA）、Sanger测序并结合文献复习分析相关特征。结果羊水核型分析结果为46,XY，母体DNA污染检测阴性；STR分型显示胎儿13号及21号染色体呈三峰模式（峰高约为2∶1∶1），家系比对证实该结果来源于1种母源等位基因及2种父源等位基因；CMA明确胎儿存在两种46,XY细胞系，各占50%即为46,XY/46,XY异源嵌合体；Sanger测序结果证实胎儿携带了四肽重复序列结构域7A基因（tetratricopeptide repeat domain 7A,TTC7A）复合杂合变异；超声检查提示胎儿存在多发发育异常。结论 STR与CMA联合应用可有效诊断46,XY/46,XY异源嵌合体；本例嵌合体可能是母亲生殖细胞孤雌分裂产生双卵子，分别与同一父亲Y染色体基因型不同的精子结合形成双受精卵后胚胎融合而成，临床需结合不良孕产史及单基因变异特征开展遗传咨询。更多还原

【Abstract】 Objective To explore the prenatal diagnostic strategy,molecular mechanism,and clinical prognosis of a rare chimerism combined with a monogenic mutation,providing evidence-based insights for genetic counseling and management.Methods A comprehensive workup was performed for a pregnant woman with an adverse reproductive history.The strategy integrated ultrasonography,familial short tandem repeat(STR)analysis,maternal DNA contamination testing,chromosomal karyotyping,chromosomal microarray analysis(CMA),and Sanger sequencing.A literature review was conducted to analyze related characteristics.Results The result of amniotic fluid karyotype analysis was 46,XY,and the maternal DNA contamination test was negative.STR genotyping showed that the fetus’ s chromosomes 13 and 21 presented a three-peak pattern(with a peak ratio of2∶1∶1),and pedigree comparison confirmed that this result originated from 1 type of maternal allele and 2 types of paternal alleles.CMA confirmed that the fetus had two 46,XY cell lines,each accounting for 50%,which was identified as 46,XY/46,XY heterologous chimera.Sanger sequencing results confirmed that the fetus carried compound heterozygous variants in the tetratricopeptide repeat domain 7 Agene(TTC7A).Ultrasonography indicated that the fetus had multiple developmental abnormalities.Conclusion Combined application of STR and CMA can effectively diagnose 46,XY/46,XY heterologous chimera.This chimera in the present case may have originated from the parthenogenetic division of the mother’s germ cells to produce two ova,which then combined with sperm(from the same father)with different Y chromosome genotypes to form two zygotes,followed by embryonic fusion.Clinically,genetic counseling should be conducted in combination with the patient’s adverse pregnancy and childbirth history and monogenic variant characteristics.更多还原