ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1675663
Prenatal Diagnosis of Prader-Willi Syndrome via Maternal UPD15 with Placental Mosaicism: Incidental Discovery of Fetal DMD Carrier Status
Provisionally accepted
- Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
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Background Prader-Willi syndrome (PWS) represents a paradigm of genomic imprinting disorders. Given the severe lifelong complications of PWS, prenatal diagnosis is crucial for early intervention and genetic counseling. Methods Noninvasive prenatal testing (NIPT) indicated a high risk for fetal trisomy 15 (T15), prompting confirmatory invasive testing. Amniocentesis was performed, and amniotic fluid was analyzed by karyotyping, chromosomal microarray analysis (CMA), trio-based whole-exome sequencing (trio-WES), and short tandem repeat (STR) linkage analysis to investigate the genetic etiology. Post-termination, placental tissue was analyzed by copy number variant sequencing (CNVseq) to evaluate potential mosaicism. Results NIPT indicated a suspected T15 (Z-score: 16.4). Subsequent invasive testing confirmed the following: a 13.16 Mb region of homozygosity on chromosome 15q25.1q26.1, and a 273 kb Duchenne muscular dystrophy (DMD) gene deletion on chromosome Xp21.1, both identified by CMA. Trio-WES and STR linkage analysis revealed maternal segmental uniparental disomy of chromosome 15 (UPD15), confirming the genetic basis of PWS. Post-termination, CNVseq further demonstrated confined placental mosaicism (CPM) for T15. Conclusions When NIPT suggests a high risk of T15, clinicians should maintain a high suspicion for the "trisomy rescue" mechanism, where an initially trisomic zygote undergoes mitotic correction, ultimately forming UPD15 with CPM. The potential discordance between NIPT and the actual fetal genetic status necessitates definitive prenatal diagnosis, which has critical implications for subsequent pregnancy management. Therefore, the concomitant findings of PWS and DMD carrier status require comprehensive prognostic evaluation and recurrence risk assessment.
Keywords: T15, UPD15, Prader-Willi Syndrome, DMD, Prenatal Diagnosis, Confined placental mosaicism, Duchenne muscular dystrophy
Received: 29 Jul 2025; Accepted: 18 Sep 2025.
Copyright: © 2025 Ye, Fu, Zhang, Ning, Tao, Wang, Fang, Chen and Hao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiulan Hao, haoxiulan@sysush.com
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