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Review
. 2020 Oct;8(10):e1448.
doi: 10.1002/mgg3.1448. Epub 2020 Aug 28.

Prenatal diagnosis of Prader-Willi syndrome due to uniparental disomy with NIPS: Case report and literature review

Jekaterina Shubina  1 , Ilya Y Barkov  1 , Olga K Stupko  1 , Maria V Kuznetsova  1 , Andrey Y Goltsov  1 , Taisya O Kochetkova  1 , Dmitry Y Trofimov  1 , Gennady T Sukhikh  1
Affiliations
Review

Prenatal diagnosis of Prader-Willi syndrome due to uniparental disomy with NIPS: Case report and literature review

Jekaterina Shubina et al. Mol Genet Genomic Med. 2020 Oct.

Abstract

Background: PWS is challenging to diagnose prenatally due to a lack of precise and well-characterized fetal phenotypes and noninvasive markers. Here we present the case of prenatal diagnosis of Prader-Willi syndrome, which was suspected with whole-genome NIPS.

Methods: Whole-genome noninvasive prenatal screening showed a high risk for trisomy 15. Amniocentesis followed by FISH analysis and SNP-based chromosomal microarray was performed.

Results: Simultaneous analysis of maternal and fetal samples with SNP microarrays demonstrated maternal uniparental disomy (UPD).

Conclusion: The presented case is the first case of PWS described in detail, which was suspected by NIPS results. It demonstrates that the choice of confirmation methods concerning the time needed is crucial for the right diagnosis. We suppose that prenatal testing of UPD is essential for chromosome regions, which play a key role in the appearance of various gene-imprinting failure syndromes like PWS or AS.

Keywords: NIPS; Prader-Willi syndrome; UPD; rare trisomy; trisomy 15.

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Conflict of interest statement

All authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
NIPS results revealed high risk for trisomy 15.
Figure 2
Figure 2
Molecular karyotyping arr[hg19] 15q26.2q26.3(95 806 550‐102 395 843)x2 hmz.
Figure 3
Figure 3
Comparison of maternal and fetal genotypes for chromosome 15. Solid line‐fraction of genotypes within 50 SNP‐window where both alleles are identical to the maternal allele demonstrates the presence of maternal heterodisomy in the 15q11.1q26.2 region. Dash line‐fraction of homozygous genotypes in fetus within 50 SNP‐window demonstrates the presence of loss of heterozygosity region on the end of the chromosome.
Figure 4
Figure 4
T‐peak raw data in SeQMA analysis. Capillary electropherograms of T‐peaks in the SNRPN‐promoter region are used for the SeQMA assay on bisulfite‐treated DNA. Arrows indicate cytosine residues in CpG dinucleotides of the original sequence. Other peaks were either original thymine or non‐CpG cytosine residues. (a) Hypermethylated CpG cytosines in DNA from a PWS patient escape bisulfite transformation and no peak signal is generated in the SeQMA assay (b) Control DNA showing a 50% reduction in peak signal indicating one methylated allele.
See this image and copyright information in PMC

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