Mosaic genome-wide paternal uniparental disomy after discordant results from primary fetal samples and cultured cells.
Beckwith-Wiedemann syndrome
MS-MLPA
SNP-array
genome-wide androgenetic mosaicism
genome-wide paternal uniparental disomy
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
15
12
2022
received:
14
02
2022
accepted:
21
12
2022
pubmed:
5
1
2023
medline:
15
3
2023
entrez:
4
1
2023
Statut:
ppublish
Résumé
Mosaic genome-wide paternal uniparental disomy (GWpUPD) is a rare condition in which two euploid cell lines coexist in the same individual, one with biparental content and one with genome-wide paternal isodisomy. We report a complex prenatal diagnosis with discordant results from cultured and uncultured samples. A pregnant woman was referred for placental mesenchymal dysplasia and fetal omphalocele. Karyotype, array-CGH and Beckwith-Wiedemann Syndrome (BWS) testing (methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) of 11p15) performed on amniocytes were negative. After intrauterine fetal demise, the clinical suspicion persisted and BWS MS-MLPA was repeated on cultured cells from umbilical cord and amniotic fluid, revealing a mosaicism for KvH19 hypermethylation/KCNQ1OT1:TSS:DMR hypomethylation. These results, along with microsatellite analysis of the BWS region, were consistent with mosaic paternal 11p15 isodisomy. A concurrent maternal contamination exclusion test, analyzing polymorphic microsatellite markers on multiple chromosomes, showed an imbalance in favor of paternal alleles at all examined loci on cultured amniocytes and umbilical cord samples. This led to suspicion of mosaic GWpUPD, later confirmed by SNP-array, identifying a mosaic genome-wide paternal isodisomy affecting 60% of fetal cells. The assessment of mosaic GWpUPD requires multiple approaches beyond the current established diagnostic processes, also entertaining possible low-rate mosaicism. Clinical acumen and an integrated testing approach are the key to a successful diagnosis.
Identifiants
pubmed: 36598152
doi: 10.1002/ajmg.a.63112
doi:
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
1101-1106Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
Borgulová, I., Soldatova, I., Putzová, M., Malíková, M., Neupauerová, J., Marková, S. P., Trková, M., & Seeman, P. (2018). Genome-wide uniparental diploidy of all paternal chromosomes in an 11-year-old girl with deafness and without malignancy. Journal of Human Genetics, 63(7), 803-810. https://doi.org/10.1038/s10038-018-0444-9
Brioude, F., Kalish, J. M., Mussa, A., Foster, A. C., Bliek, J., Ferrero, G. B., Boonen, S. E., Cole, T., Baker, R., Bertoletti, M., Cocchi, G., Coze, C., De Pellegrin, M., Hussain, K., Ibrahim, A., Kilby, M. D., Krajewska-Walasek, M., Kratz, C. P., Ladusans, E. J., … Maher, E. R. (2018). Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: An international consensus statement. Nature Reviews. Endocrinology, 14(4), 229-249. https://doi.org/10.1038/nrendo.2017.166
Bryke, C.R., Garber, A.T., Israel, J. (2004). Evolution of a complex phenotype in a unique patient with a paternal uniparental disomy for every chromosome cell line and a normal biparental inheritance cell line. Presented at the annual meeting of the American Society of Human Genetics, Toronto, Canada: http://www.ashg.org/genetics/ashg/annmeet/2004/menu-annmeet-2004.shtml
Butler, M. G. (2020). Imprinting disorders in humans: A review. Current Opinion in Pediatrics, 32(6), 719-729. https://doi.org/10.1097/MOP.0000000000000965
Christesen, H. T., Christensen, L. G., Löfgren, Å. M., Brøndum-Nielsen, K., Svensson, J., Brusgaard, K., Samuelsson, S., Elfving, M., Jonson, T., Grønskov, K., Rasmussen, L., Backman, T., Hansen, L. K., Larsen, A. R., Petersen, H., & Detlefsen, S. (2020). Tissue variations of mosaic genome-wide paternal uniparental disomy and phenotype of multi-syndromal congenital hyperinsulinism. European Journal of Medical Genetics, 63(1), 103632. https://doi.org/10.1016/j.ejmg.2019.02.004
Conlin, L. K., Thiel, B. D., Bonnemann, C. G., Medne, L., Ernst, L. M., Zackai, E. H., Deardorff, M. A., Krantz, I. D., Hakonarson, H., & Spinner, N. B. (2010). Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis. Human Molecular Genetics, 19(7), 1263-1275. https://doi.org/10.1093/hmg/ddq003
Eggermann, T., Brioude, F., Russo, S., Lombardi, M. P., Bliek, J., Maher, E. R., Larizza, L., Prawitt, D., Netchine, I., Gonzales, M., Grønskov, K., Tümer, Z., Monk, D., Mannens, M., Chrzanowska, K., Walasek, M. K., Begemann, M., Soellner, L., Eggermann, K., … Lapunzina, P. (2016). Prenatal molecular testing for Beckwith-Wiedemann and silver-Russell syndromes: A challenge for molecular analysis and genetic counseling. European Journal of Human Genetics: EJHG, 24(6), 784-793. https://doi.org/10.1038/ejhg.2015.224
Elbracht, M., Mackay, D., Begemann, M., Kagan, K. O., & Eggermann, T. (2020). Disturbed genomic imprinting and its relevance for human reproduction: Causes and clinical consequences. Human Reproduction Update, 26(2), 197-213. https://doi.org/10.1093/humupd/dmz045
Guenot, C., Kingdom, J., de Rham, M., Osterheld, M., Keating, S., Vial, Y., Van Mieghem, T., Jastrow, N., Raio, L., Spinelli, M., Di Meglio, L., Chalouhi, G., & Baud, D. (2019). Placental mesenchymal dysplasia: An underdiagnosed placental pathology with various clinical outcomes. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 234, 155-164. https://doi.org/10.1016/j.ejogrb.2019.01.014
Hoban, P. R., Heighway, J., White, G. R., Baker, B., Gardner, J., Birch, J. M., Morris-Jones, P., & Kelsey, A. M. (1995). Genome-wide loss of maternal alleles in a nephrogenic rest and Wilms' tumour from a BWS patient. Human Genetics, 95(6), 651-656. https://doi.org/10.1007/BF00209482
Inbar-Feigenberg, M., Choufani, S., Cytrynbaum, C., Chen, Y. A., Steele, L., Shuman, C., Ray, P. N., & Weksberg, R. (2013). Mosaicism for genome-wide paternal uniparental disomy with features of multiple imprinting disorders: Diagnostic and management issues. American Journal of Medical Genetics. Part A, 161A(1), 13-20. https://doi.org/10.1002/ajmg.a.35651
Kalish, J. M., Conlin, L. K., Bhatti, T. R., Dubbs, H. A., Harris, M. C., Izumi, K., Mostoufi-Moab, S., Mulchandani, S., Saitta, S., States, L. J., Swarr, D. T., Wilkens, A. B., Zackai, E. H., Zelley, K., Bartolomei, M. S., Nichols, K. E., Palladino, A. A., Spinner, N. B., & Deardorff, M. A. (2013). Clinical features of three girls with mosaic genome-wide paternal uniparental isodisomy. American Journal of Medical Genetics. Part A, 161A(8), 1929-1939. https://doi.org/10.1002/ajmg.a.36045
Keren, B., Chantot-Bastaraud, S., Brioude, F., Mach, C., Fonteneau, E., Azzi, S., Depienne, C., Brice, A., Netchine, I., Le Bouc, Y., Siffroi, J. P., & Rossignol, S. (2013). SNP arrays in Beckwith-Wiedemann syndrome: An improved diagnostic strategy. European Journal of Medical Genetics, 56(10), 546-550. https://doi.org/10.1016/j.ejmg.2013.06.005
Monk, D., Mackay, D. J. G., Eggermann, T., Maher, E. R., & Riccio, A. (2019). Genomic imprinting disorders: Lessons on how genome, epigenome and environment interact. Nature Reviews. Genetics, 20(4), 235-248. https://doi.org/10.1038/s41576-018-0092-0
Postema, F. A. M., Bliek, J., van Noesel, C. J. M., van Zutven, L. J. C. M., Oosterwijk, J. C., Hopman, S. M. J., Merks, J. H. M., & Hennekam, R. C. (2019). Multiple tumors due to mosaic genome-wide paternal uniparental disomy. Pediatric Blood & Cancer, 66(6), e27715. https://doi.org/10.1002/pbc.27715
Repnikova, E., Roberts, J., Kats, A., Habeebu, S., Schwager, C., Joyce, J., Manalang, M., & Amudhavalli, S. M. (2018). Biparental/androgenetic mosaicism in a male with features of overgrowth and placental mesenchymal dysplasia. Clinical Genetics, 94(6), 564-568. https://doi.org/10.1111/cge.13431
Robinson, W. P., Lauzon, J. L., Innes, A. M., Lim, K., Arsovska, S., & McFadden, D. E. (2007). Origin and outcome of pregnancies affected by androgenetic/biparental chimerism. Human Reproduction, 22(4), 1114-1122. https://doi.org/10.1093/humrep/del462
Sheppard, S. E., Lalonde, E., Adzick, N. S., Beck, A. E., Bhatti, T., De Leon, D. D., Duffy, K. A., Ganguly, A., Hathaway, E., Ji, J., Linn, R., Lord, K., Randolph, L. M., Sajorda, B., States, L., Conlin, L. K., & Kalish, J. M. (2019). Androgenetic chimerism as an etiology for Beckwith-Wiedemann syndrome: Diagnosis and management. Genetics in medicine: official journal of the American College of Medical Genetics, 21(11), 2644-2649. https://doi.org/10.1038/s41436-019-0551-9
Wang, K. H., Kupa, J., Duffy, K. A., & Kalish, J. M. (2020). Diagnosis and Management of Beckwith-Wiedemann Syndrome. Frontiers in Pediatrics, 7, 562. https://doi.org/10.3389/fped.2019.00562
Wilson, M., Peters, G., Bennetts, B., McGillivray, G., Wu, Z. H., Poon, C., & Algar, E. (2008). The clinical phenotype of mosaicism for genome-wide paternal uniparental disomy: Two new reports. American Journal of Medical Genetics. Part A, 146A(2), 137-148. https://doi.org/10.1002/ajmg.a.32172