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Usefulness of methylation-specific multiplex ligation-dependent probe amplification for identification of parental origin of triploidy

Journal of Human Genetics volume 65, pages 889–894 (2020)Cite this article

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Abstract

Triploidy is a genetic aberration resulting from an extra haploid set of chromosomes of paternal (diandric) or maternal (digynic) origin. Diandric cases, opposite to digynic ones, may lead to gestational trophoblastic neoplasia (GTN) or generate maternal complications, therefore their identification is crucial, but reproducibility of traditionally used histopathological assessment is poor. The aim of the study was to analyse the usefulness of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) with probes for two differentially methylated regions (DMR) at chromosome 11p.15.5 for identification of the parental origin of triploidy. 84 triploid DNA samples were tested with MS-MLPA: 34 paternal cases (40.5%) and 50 maternal ones (59.5%) according to the reference results of QF-PCR. Methylation ratio (MR) was calculated. Reference values proposed by the MRC-Holland for diploid samples (MR 0.8–1.2) were used. The values outside these ranges were used to diagnose parental origin of triploidy—paternal (MR > 1.2) or maternal (MR < 0.8). The effectiveness of MS-MLPA was 94.0%. The mean MR in paternal triploidy was 1.7 (SD–0.25; n = 34) compared with 0.56 in maternal triploidy (SD–0.12; n = 50). MR values in paternal and maternal triploidy did not overlap. In five samples (6.0%) parental origin of triploidy could not be accurately established by MS-MLPA, probably due to the maternal cell contamination (MCC). MS-MLPA can be used as a convenient method for distinguishing between paternal and maternal triploidy without the necessity for parental samples testing. It enables adequate selection of the paternal triploid cases for follow up in order to exclude post-molar GTN.

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Funding

The study was partly funded by Centre of Postgraduate Medical Education in Warsaw (Project No. 501-1-21-27-18).

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Authors and Affiliations

  1. Department of Gynecologic Oncology and Obstetrics, Centre of Postgraduate Medical Education, Czerniakowska 231, 00-416, Warsaw, Poland

    Diana Massalska, Julia Bijok, Tomasz Roszkowski, Anna Kucińska-Chahwan & Grzegorz Mieczysław Panek

  2. Department of Genetics, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957, Warsaw, Poland

    Katarzyna Ozdarska & Janusz Grzegorz Zimowski

  3. Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, Żelazna 90, 01-004, Warsaw, Poland

    Grzegorz Jakiel

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  1. Diana Massalska
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  2. Katarzyna Ozdarska
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  4. Tomasz Roszkowski
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  8. Janusz Grzegorz Zimowski
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Correspondence to Diana Massalska.

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Massalska, D., Ozdarska, K., Bijok, J. et al. Usefulness of methylation-specific multiplex ligation-dependent probe amplification for identification of parental origin of triploidy. J Hum Genet 65, 889–894 (2020). https://doi.org/10.1038/s10038-020-0784-0

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