13q21大片段缺失二家系胎儿的产前诊断和遗传学咨询研究

Prenatal diagnosis and genetic analysis for two Chinese pedigrees carrying large fragment deletions of 13q21

目的探讨2个13q21大片段缺失家系胎儿的产前诊断和遗传学咨询策略。方法选择2021年3月、2021年12月于宁波市妇女儿童医院产前诊断门诊确诊为胎儿13号染色体大片段缺失的2例单胎妊娠胎儿(胎儿1、2)为研究对象。2例胎儿母亲均完善羊水穿刺,对胎儿1、2进行染色体核型分析和染色体微阵列分析(CMA),并采集胎儿父母的外周血样进行CMA检测,追溯胎儿异常染色体的来源。结果胎儿1、2的染色体核型均未见明显异常。CMA检测结果提示胎儿1、2分别携带母源性13q21.1q21.33区段11.935 Mb、父源性13q14.3q21.32区段10.995 Mb的杂合缺失。胎儿1、2的2个缺失的片段基因密度低,缺乏单倍剂量敏感基因,数据库检索缺乏有效数据,均判断为可能良性变异,2例胎儿父母均选择继续妊娠。结论本研究发现2个家系胎儿1、2的13q21区段缺失可能为良性变异,由于未进行足够长时间的随访研究,而且仅为病例研究,所以是否存在致病性尚没有充分证据,但是或许可为临床产前诊断和遗传咨询提供一定依据。

Objective To explore the strategies of prenatal diagnosis and genetic counseling for fetuses of two families with large deletions of 13q21.Methods Two singleton fetuses who were diagnosed with chromosome 13 microdeletions by non-invasive prenatal testing(NIPT)at Ningbo Women and Children′s Hospital in March 2021 and December 2021 respectively were selected as the study subjects.Chromosomal karyotyping and chromosomal microarray analysis(CMA)were carried on amniotic samples.Peripheral blood samples were collected from the two couples for CMA assay to determine the origin of abnormal chromosomes identified in the fetuses.Results The karyotypes of the two fetuses were both normal.CMA revealed that they have respectively harbored heterozygous deletions spanning 11.935 Mb at 13q21.1q21.33 and 10.995 Mb at 13q14.3q21.32,which were respectively inherited from their mother and father.Both deletions had low gene density and lacked haploinsufficient genes,and were predicted to be likely benign variants based on database and literature search.Both couples had opted to continue with the pregnancy.Conclusion The deletions of the 13q21 region in both families may be of benign variants.As the follow-up time was short,there was no sufficient evidence for the determination of pathogenicity,though our finding may still provide a basis for the prenatal diagnosis and genetic counseling.