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Genome-wide uniparental diploidy of all paternal chromosomes in an 11-year-old girl with deafness and without malignancy


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.

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This study was supported by the Czech Ministry of Health AZV 16-31173A and DRO 00064203.

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Correspondence to Irena Borgulová.

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The experiments presented in this manuscript were conducted in accordance with law of the Czech Republic.

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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).

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