A Xp22.11-p21.3 microdeletion in a three-generation family supports male lethality of POLA1 nullisomy resulting in reduced fertility of female carriers
| Autor: | Begemann, Anaïs, Oneda, Beatrice, Baumer Wolz, Alessandra, Guldimann, Marina, Tutschek, Boris, Rauch, Anita |
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| Přispěvatelé: | University of Zurich |
| Rok vydání: | 2022 |
| Předmět: |
Male
Heterozygote 10039 Institute of Medical Genetics DNA polymerase alpha 610 Medicine & health Genetic Diseases X-Linked General Medicine DNA Polymerase I POLA1 Van Esch Fertility 10036 Medical Clinic early pregnacy loss Genes X-Linked Intellectual Disability Genetics 570 Life sciences biology Humans Female O’Driscoll syndrome Genetics (clinical) |
| DOI: | 10.5167/uzh-220921 |
| Popis: | POLA1 encodes a subunit of the DNA polymerase alpha, a key enzyme for the initiation of DNA synthesis. In males, hemizygous hypomorphic variants in POLA1 have been identified as the cause of X-linked pigmentary reticulate disorder (XLPDR) and a novel X-linked neurodevelopmental disorder termed Van Esch-O'Driscoll syndrome (VEODS), while female carriers have been reported to be healthy. Nullisomy for POLA1 was speculated to be lethal due to its crucial function, while the effect of loss of one allele in females remained unknown. Here, we report on a three-generation family harboring a deletion of POLA1 in females showing subfertility as the only phenotype. Our findings show that heterozygous deletions or truncating variants in females with skewed X inactivation do not cause VEODS and support the hypothesis of very early embryonic lethality in males with POLA1 nullisomy. |
| Databáze: | OpenAIRE |
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