Prenatal diagnosis of mosaic chromosomal aneuploidy and uniparental disomy and clinical outcomes evaluation of four fetuses.

IF 1.3 4区生物学 Q4 GENETICS & HEREDITY Molecular Cytogenetics Pub Date : 2023-12-06 DOI:10.1186/s13039-023-00667-9

Shengfang Qin, Xueyan Wang, Jin Wang, Na Xi, Mengjia Yan, Yuxia He, Mengling Ye, Zhuo Zhang, Yan Yin

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Abstract

Background: Few co-occurrence cases of mosaic aneuploidy and uniparental disomy (UPD) chromosomes have been reported in prenatal periods. It is a big challenge for us to predict fetal clinical outcomes with these chromosome abnormalities because of their highly heterogeneous clinical manifestations and limited phenotype attainable by ultrasound.

Methods: Amniotic fluid samples were collected from four cases. Karyotype, chromosome microarray analysis, short tandem repeats, and whole exome sequencing were adopted to analyze fetal chromosomal aneuploidy, UPD, and gene variation. Meanwhile, CNVseq analysis proceeded for cultured and uncultured amniocytes in case 2 and case 4 and MS-MLPA for chr11 and chr15 in case 3.

Results: All four fetuses showed mosaic chromosomal aneuploidy and UPD simultaneously. The results were: Case 1: T2(7%) and UPD(2)mat(12%). Case 2: T15(60%) and UPD(15)mat(40%). Case 3: 45,X(13%) and genome-wide paternal UPD(20%). Case 4: <10% of T20 and > 90% UPD(20)mat in uncultured amniocyte. By analyzing their formation mechanism of mosaic chromosomal aneuploidy and UPD, at least two adverse genetic events happened during their meiosis and mitosis. The fetus of case 1 presented a benign with a normal intrauterine phenotype, consistent with a low proportion of trisomy cells. However, the other three fetuses had adverse pregnancy outcomes, resulting from the UPD chromosomes with imprinted regions involved or a higher level of mosaic aneuploidy.

Conclusion: UPD is often present with mosaic aneuploidy. It is necessary to analyze them simultaneously using a whole battery of analyses for these cases when their chromosomes with imprinted regions are involved or known carriers of a recessive allele. Fetal clinical outcomes were related to the affected chromosomes aneuploidy and UPD, mosaic levels and tissues, methylation status, and homozygous variation of recessive genes on the UPD chromosome. Genetic counseling for pregnant women with such fetuses is crucial to make informed choices.

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4例胎儿马赛克染色体非整倍体和孤本二体的产前诊断及临床预后评价。

背景:产前染色体嵌合非整倍体和单系二体(UPD)同时出现的病例很少。对我们来说，预测这些染色体异常的胎儿临床结果是一个很大的挑战，因为它们的临床表现高度异质性，超声可获得的表型有限。方法:采集4例羊水标本。采用核型分析、染色体微阵列分析、短串联重复序列和全外显子组测序分析胎儿染色体非整倍体、UPD和基因变异。同时，对病例2和病例4的培养和未培养羊膜细胞进行CNVseq分析，对病例3的chr11和chr15进行MS-MLPA分析。结果:4例胎儿同时出现马赛克染色体非整倍体和UPD。结果为:病例1:T2(7%)和UPD(2)mat(12%)。病例2:T15(60%)和UPD(15)mat(40%)。病例3:45,x(13%)和全基因组父系UPD(20%)。病例4:未培养羊膜细胞90% UPD(20)。通过分析它们的花叶染色体非整倍体和UPD的形成机制，发现它们在减数分裂和有丝分裂过程中至少发生了两次不良遗传事件。病例1胎儿呈良性，宫内表型正常，与三体细胞比例低一致。然而，其他三个胎儿的妊娠结局不良，这是由于UPD染色体有印迹区域参与或更高水平的马赛克非整倍体。结论:UPD常表现为花叶非整倍体。当它们的带有印迹区域的染色体是隐性等位基因的携带者或已知的携带者时，有必要同时使用一整套分析方法对它们进行分析。胎儿临床结局与受影响染色体的非整倍性和UPD、镶嵌水平和组织、甲基化状态、UPD染色体上隐性基因的纯合变异有关。对有这种胎儿的孕妇进行遗传咨询对于做出明智的选择至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cytogenetics GENETICS & HEREDITY-

CiteScore

2.60

自引率

7.70%

发文量

审稿时长

>12 weeks

期刊介绍： Molecular Cytogenetics encompasses all aspects of chromosome biology and the application of molecular cytogenetic techniques in all areas of biology and medicine, including structural and functional organization of the chromosome and nucleus, genome variation, expression and evolution, chromosome abnormalities and genomic variations in medical genetics and tumor genetics. Molecular Cytogenetics primarily defines a large set of the techniques that operate either with the entire genome or with specific targeted DNA sequences. Topical areas include, but are not limited to: -Structural and functional organization of chromosome and nucleus- Genome variation, expression and evolution- Animal and plant molecular cytogenetics and genomics- Chromosome abnormalities and genomic variations in clinical genetics- Applications in preimplantation, pre- and post-natal diagnosis- Applications in the central nervous system, cancer and haematology research- Previously unreported applications of molecular cytogenetic techniques- Development of new techniques or significant enhancements to established techniques. This journal is a source for numerous scientists all over the world, who wish to improve or introduce molecular cytogenetic techniques into their practice.