Approximately 20 cases of genome-wide uniparental disomy or diploidy (GWUPD) as mosaicism have previously been reported. We present the case of an 11-year-old deaf girl with a paternal uniparental diploidy or isodisomy with a genome-wide loss of heterozygosity (LOH). The patient was originally tested for non-syndromic deafness, and the novel variant p.V234I in the ESRRB gene was found in a homozygous state. Our female proband is the seventh patient diagnosed with GWUPD at a later age and is probably the least affected of the seven, as she has not yet presented any malignancy. Most, if not all, reported patients with GWUPD whose clinical details have been published have developed malignancy, and some of those patient developed malignancy several times. Therefore, our patient has a high risk of malignancy and is carefully monitored by a specific outpatient pediatric oncology program. This observation seems to be novel and unique in a GWUPD patient. Our study is also unique as it not only provides very detailed documentation of the genomic situations of various tissues but also reports differences in the mosaic ratios between the blood and saliva, as well as a normal biparental allelic situation in the skin and biliary duct. Additionally, we were able to demonstrate that the mosaic ratio in the blood remained stable even after 3 years and has not changed over a longer period.
Subscribe to Journal
Get full journal access for 1 year
only $33.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Yamazawa K, Ogata T, Ferguson-Smith AC. Uniparental disomy and human disease. Am J Med Genet Part C Semin Med Genet. 2010;154C:329–34.
Conlin LK, Thiel BD, Bonnemann CG, Medne L, Ernst LM, Zackai EH, et al. Mechanism of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis. Hum Mol Genet. 2010;19:1263–75.
Engel E. A fascination with chromosome rescue in uniparental disomy: Mendelian recessive outlaws and imprinting copyrights infringements. Eur J Hum Genet. 2006;14:1154–69.
Robinson WP. Mechanisms leading to uniparental disomy and their clinical consequences. Bioessays. 2000;22:452–9.
Kalish JM, Conlin LK, Bhatti TR, Dubbs HA, Harris MC, Izumi K, et al. Clinical features of three girls with mosaic genome-wide paternal uniparental isodisomy. Am J Med Genet. 2013;1161:1929–39.
Biesecker LG, Spinner NB. A genomic view of mosaicism and human disease. Nat Rev. 2013;14:307–14.
Strachan T, Read AP. Human molecular genetics. Garland Science, New York, USA, 2011.
Cotran RS, Kumar V, Fausto N, Nelso F, Robbins SL, Abbas AK. Robbins and Cotran pathologic basis of disease. 7th edn. Elsevier Saunders, Chicago, USA, 2005.
Kumar V, Abbas KA, Fausto N, Aster J. Robbins and Cotran pathologic basis of disease. 8th edn. Elsevier Saunders, Philadelphia, USA, 2010.
Fentom TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:59.
Putzová M, Pecnová L, Dvořaková L, Soldatova I, Goetz P, Stejskal D. OmniPlex – a new QF-PCR assay for prenatal diagnosis of common aneuploidies based on evaluation of the heterozygosity of short tandem repeat loci in the Czech population. Prenat Diagn. 2008;28:1214–20.
Hoban PR, Heighway J, White GR, Baker B, Gardner J, Birch JM, et al. Genome-wide loss of maternal alleles in a nephrogenic rest and Wilms’ tumour from a BWS patient. Hum Genet. 1995;95:651–6.
Gogiel M, Begemann M, Spengler S, Soellner L, Göretzlehner U, Eggermann T, et al. Genome-wide paternal uniparental disomy mosaicism in a woman with Beckwith–Wiedemann syndrome and ovarian steroid cell tumour. Eur J Hum Genet. 2013;21:788–91.
Bertoin F, Letouzé E, Grignani P, Patey M, Rossignol S, Libé R, et al. Genome-wide paternal uniparental disomy as a cause of Beckwith-Wiedemann syndrome associated with recurrent virilizing adrenocortical tumors. Horm Metab Res. 2015;47:497–503.
Darcy D, Atwal PS, Angell C, Gadi I, Wallerstein R. Mosaic paternal genome-wide uniparental isodisomy with Down syndrome. Am J Med Genet. 2015;167:2463–9.
Bryke CR, Garber AT, Israel J. 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. Am J Hum Genet. 2004, http://www.ashg.org/genetics/abstracts/abs04/f823.htm.
Giurgea I, Sanlaville D, Fournet JC, Sempoux C, Bellanné- Chantelot C, Touati G, et al. Congenital hyperinsulinism and mosaic abnormalities of the ploidy. J Med Genet. 2006;43:248–54.
Reed RC, Beischel L, Schoof J, Johnson J, Raff ML, Kapur RP. Androgenetic/biparental mosaicism in an infant with hepatic mesenchymal hamartoma and placental mesenchymal dysplasia. Pediatr Dev Pathol. 2008;11:377–83.
Wilson M, Peters G, Bennetts B, McGillivray G, Wu ZH, Poon C, et al. The clinical phenotype of mosaicism for genome-wide paternal uniparental disomy: two new reports. Am J Med Genet. 2008;146A:137–48.
Romanelli V, Nevado J, Fraga M, Trujillo AM, Mori MA, Fernandez L, et al. Constitutional mosaic genome-wide uniparental disomy due to diploidisation: An unusual cancer-predisposing mechanism. J Med Genet. 2011;48:212–6.
Yamazawa K, Nakabayashi K, Matsuoka K, Masubara K, Hata K, Horikawa R, et al. Androgenetic/biparental mosaicism in a girl with Beckwith–Wiedemann syndrome-like and upd(14)pat-like phenotypes. J Hum Genet. 2011;56:91–93.
Inbar-Feigenberg M, Choufani S, Cytrynbaum C, Chen YA, Steele L, Shuman C, et al. Mosaicism for genome-wide paternal uniparental disomy with features of multiple imprinting disorders: diagnostic and management issues. Am J Med Genet Part A. 2013;161A:13–20.
Azmanov D, Edwards C, Stampalia J, Carpenter K, Woodward K, Mina K. Mosaic genome-wide uniparetnal disomy (GW-UPD): heterogeneity of a rare disorder popes diagnostic and management challenges. Pathology. 2014;46:S91.
Ohtsuka Y, Higashimoto K, Sasaki K, Jozaki K, Yoshinaga H, Okamoto N, et al. Autosomal recessive cystinuria caused by genome-wide paternal uniparental isodisomy in a patient with Beckwith-Wiedemann syndrome. Clin Genet. 2015;88:261–6.
Ohtsuka Y, Higashimoto K, Oka T, Yatsuki H, Jozaki K, Maeda T, et al. Identification of consensus motifs associated with mitotic recombination and clinical characteristics in patients with paternal uniparental isodisomy of chromosome 11. Hum Mol Genet. 2016;25:1406–19.
Yamazawa K, Nakabayashi K, Kagami M, Sato T, Saitoh S, Horikawa R, et al. Parthenogenetic chimaerism/mosaicism with a Silver-Russell syndrome-like phenotype. J Med Genet. 2010;47:782–5.
Engel E. A new genetic concept: the uniparental disomy and its potential effect, the isodisomy. J Genet Hum. 1980;28:11–22.
Berend SA, Feldman GL, McCaskill C, Czarnecki P, Van Dyke DL, Shaffer LG. Investigation of two cases of paternal disomy 13 suggests timing of isochromosome formation and mechanisms leading to uniparental disomy. Am J Med Genet. 1999;82:275–81.
Kaiser-Rogers JA, McFadden DE, Livasy C, Dansereau J, Jiang R, Knops JF, et al. Androgenetic/biparental mosaicism causes placental mesenchymal dysplasia. J Med Genet. 2006;43:187–92.
Munné S, Weier HU, Grifo J, Cohen J. Chromosome mosaicism in human embryos. Biol Reprod. 1994;51:373–9.
Harper JC, Coonen E, Handyside AH, Winston RM, Hopman AH, Delhanty JD. Mosaicism of autosomes and sex chromosomes in morphologically normal, monospermic preimplantation human embryos. Prenat Diagn. 1995;15:41–9.
Cohen MC, Roper EC, Sebire NJ, Stanek J, Anumba DO. Placental mesenchymal dysplasia associated with fetal aneuploidy. Prenat Diagn. 2005;25:187–92.
Surti U, Hill LM, Dunn J, Prosen T, Hoffner L. Twin pregnancy with a chimeric androgenetic and biparental placenta in one twin displaying placental mesenchymal dysplasia phenotype. Prenat Diagn. 2005;25:1048–56.
Strain L, Warner JP, Johnston T, Bonthron DT. A human parthenogenetic chimaera. Nat Genet. 1995;11:164–9.
Golubovsky MD. Postzygotic diploidization of triploids as a source of unusual cases of mosaicism, chimerism and twinning. Hum Reprod. 2003;18:236–42.
Borgulová I, Mazanec R, Sakmaryová I, Havlová M, Šafka Brožková D, Seeman P. Mosaicism for GJB1 mutation causes milder Charcot-Marie-Tooth X1 phenotype in a heterozygous man than in a manifesting heterozygous woman. Neurogenetics. 2013;14:189–95.
Jones KB, Klein OD. Oral epithelial stem cells in tissue maintenance and disease: the first steps in a long journey. Int J Oral Sci. 2013;5:121–1299.
Cianga CM, Antohe I, Constantinescu D, Cianga P. Saliva leukocytes rather than saliva epithelial cells represent the main source of DNA. Rom J Lab M. 2016;24:31–44.
Schiött CR, Löe H. The origin and variation in number of leukocytes in saliva. J Periodontal Res. 1970;5:36–41.
Larsen M, Yamada KY, Musselmann K. Systems analysis of salivary gland development and disease. Wiley Interdiscip Rev Syst Biol Med. 2010;2:670–82.
This study was supported by the Czech Ministry of Health AZV 16-31173A and DRO 00064203.
The experiments presented in this manuscript were conducted in accordance with law of the Czech Republic.
Conflict of interest
The authors declare that they have no conflict of interest.
About this article
Cite this article
Borgulová, I., Soldatova, I., Putzová, M. et al. Genome-wide uniparental diploidy of all paternal chromosomes in an 11-year-old girl with deafness and without malignancy. J Hum Genet 63, 803–810 (2018). https://doi.org/10.1038/s10038-018-0444-9
Prenatal Diagnosis (2021)
Genetics in Medicine (2019)
American Journal of Medical Genetics Part A (2019)
Characterization of Prevalence and Health Consequences of Uniparental Disomy in Four Million Individuals from the General Population
The American Journal of Human Genetics (2019)