Am J Perinatol 2025; 42(09): 1135-1140
DOI: 10.1055/a-2459-8924
Original Article

Unexpected Findings of Duchenne Muscular Dystrophy in Prenatal Screening of Chromosome Abnormality Based on Cell-Free Fetal DNA

Ganye Zhao
1   Department of Obstetrics and Gynecology, The Genetics and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
,
Lina Liu
1   Department of Obstetrics and Gynecology, The Genetics and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
,
Panlai Shi
1   Department of Obstetrics and Gynecology, The Genetics and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
,
Mingxin Gu
2   Department of Reproductive Medicine and Genetics, Pingdingshan Maternal and Child Health Hospital, Pingdingshan, China
,
Shaozhe Yang
3   Henan Key Laboratory of Fertility Protection and Aristogenesis, Luohe Central Hospital, Luohe, China
,
Xiangdong Kong
1   Department of Obstetrics and Gynecology, The Genetics and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
› Author Affiliations

Funding The work was supported by the grants from Open Research Project from Henan Key Laboratory of Fertility Protection and Aristogenesis (grant no.: SYLBHHYS2022-05); Medical Education Research Project of Henan Province (grant no.: Wjlx2022050); Science and Technology Research Program of Henan Province (grant no.: 242102311087).
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Abstract

Objective

This study aims to assess the feasibility of detecting and diagnosing Duchenne muscular dystrophy (DMD) during prenatal screening for chromosome abnormalities using cell-free fetal DNA extracted from peripheral blood samples of pregnant women.

Study Design

Two pregnant women identified as high risk through noninvasive prenatal testing (NIPT) underwent amniocentesis to obtain fetal cells. Subsequent fetal chromosomal karyotyping was conducted, and genomic DNA from fetal cells was extracted for copy number variation sequencing (CNV-Seq) analysis, complemented by multiplex ligation-dependent probe amplification (MLPA) to detect deletions or duplications within the DMD gene.

Results

NIPT results for the two samples indicated potential abnormalities involving chromosomes 21 and 18. However, karyotype analysis of the fetuses revealed no abnormalities. CNV-Seq identified deletions of 0.28 and 0.18 Mb within chromosome Xp21.1, encompassing the DMD gene, in each fetus. In family 1, MLPA results indicated a maternal heterozygous deletion spanning exons 12 to 41 in the DMD gene, while the fetus exhibited deletions in exons 12 to 41. In family 2, MLPA results confirmed normal DMD gene status in the pregnant woman's peripheral blood genomic DNA but revealed a fetal deletion spanning exons 48 to 52. Both fetuses were diagnosed with DMD and subsequently underwent termination.

Conclusion

Abnormalities identified through NIPT necessitate further invasive prenatal diagnostic procedures. For cases involving chromosomal microdeletions or microduplications, a combination of karyotyping and CNV-Seq testing is essential for comprehensive diagnosis. NIPT followed by CNV-Seq may offer insights into large exon deletions within the DMD gene in specific instances.

Key Points

  • NIPT results can offer valuable insights into the deletion and duplication of DMD gene for the fetus.

  • It's crucial to notice unexpected findings in NIPT.

  • A combination of karyotyping and CNV-Seq testing is essential for comprehensive diagnosis.

Authors' Contributions

Conceptualization: X.K., G.Z.; investigation: G.Z., L.L., P.S.; data curation: G.Z., M.G., S.Y.; experiment curation: G.Z.; writing—original draft: G.Z.; writing—review and editing: X.K.; funding acquisition: G.Z. All authors contributed to the article and approved the submitted version.


Data Availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.




Publication History

Received: 23 September 2024

Accepted: 30 October 2024

Accepted Manuscript online:
04 November 2024

Article published online:
25 November 2024

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