Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency
Adenine phosphoribosyltransferase deficiency is a rare, autosomal recessive disorder of purine metabolism that causes nephrolithiasis and progressive chronic kidney disease. The small number of reported cases indicates an extremely low prevalence, although it has been suggested that missed diagnoses...
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Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298615/ http://www.ncbi.nlm.nih.gov/pubmed/33707627 https://doi.org/10.1038/s41431-020-00805-6 |
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ftpubmed:oai:pubmedcentral.nih.gov:8298615 2023-05-15T16:47:18+02:00 Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency Runolfsdottir, Hrafnhildur L. Sayer, John A. Indridason, Olafur S. Edvardsson, Vidar O. Jensson, Brynjar O. Arnadottir, Gudny A. Gudjonsson, Sigurjon A. Fridriksdottir, Run Katrinardottir, Hildigunnur Gudbjartsson, Daniel Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari Palsson, Runolfur 2021-03-11 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298615/ http://www.ncbi.nlm.nih.gov/pubmed/33707627 https://doi.org/10.1038/s41431-020-00805-6 en eng Springer International Publishing http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298615/ http://www.ncbi.nlm.nih.gov/pubmed/33707627 http://dx.doi.org/10.1038/s41431-020-00805-6 © The Author(s), under exclusive licence to European Society of Human Genetics 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . CC-BY Eur J Hum Genet Article Text 2021 ftpubmed https://doi.org/10.1038/s41431-020-00805-6 2021-08-08T00:40:25Z Adenine phosphoribosyltransferase deficiency is a rare, autosomal recessive disorder of purine metabolism that causes nephrolithiasis and progressive chronic kidney disease. The small number of reported cases indicates an extremely low prevalence, although it has been suggested that missed diagnoses may play a role. We assessed the prevalence of APRT deficiency based on the frequency of causally-related APRT sequence variants in a diverse set of large genomic databases. A thorough search was carried out for all APRT variants that have been confirmed as pathogenic under recessive mode of inheritance, and the frequency of the identified variants examined in six population genomic databases: the deCODE genetics database, the UK Biobank, the 100,000 Genomes Project, the Genome Aggregation Database, the Human Genetic Variation Database and the Korean Variant Archive. The estimated frequency of homozygous genotypes was calculated using the Hardy-Weinberg equation. Sixty-two pathogenic APRT variants were identified, including six novel variants. Most common were the missense variants c.407T>C (p.(Met136Thr)) in Japan and c.194A>T (p.(Asp65Val)) in Iceland, as well as the splice-site variant c.400 + 2dup (p.(Ala108Glufs*3)) in the European population. Twenty-nine variants were detected in at least one of the six genomic databases. The highest cumulative minor allele frequency (cMAF) of pathogenic variants outside of Japan and Iceland was observed in the Irish population (0.2%), though no APRT deficiency cases have been reported in Ireland. The large number of cases in Japan and Iceland is consistent with a founder effect in these populations. There is no evidence for widespread underdiagnosis based on the current analysis. Text Iceland PubMed Central (PMC) European Journal of Human Genetics 29 7 1061 1070 |
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Article Runolfsdottir, Hrafnhildur L. Sayer, John A. Indridason, Olafur S. Edvardsson, Vidar O. Jensson, Brynjar O. Arnadottir, Gudny A. Gudjonsson, Sigurjon A. Fridriksdottir, Run Katrinardottir, Hildigunnur Gudbjartsson, Daniel Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari Palsson, Runolfur Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency |
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Article |
description |
Adenine phosphoribosyltransferase deficiency is a rare, autosomal recessive disorder of purine metabolism that causes nephrolithiasis and progressive chronic kidney disease. The small number of reported cases indicates an extremely low prevalence, although it has been suggested that missed diagnoses may play a role. We assessed the prevalence of APRT deficiency based on the frequency of causally-related APRT sequence variants in a diverse set of large genomic databases. A thorough search was carried out for all APRT variants that have been confirmed as pathogenic under recessive mode of inheritance, and the frequency of the identified variants examined in six population genomic databases: the deCODE genetics database, the UK Biobank, the 100,000 Genomes Project, the Genome Aggregation Database, the Human Genetic Variation Database and the Korean Variant Archive. The estimated frequency of homozygous genotypes was calculated using the Hardy-Weinberg equation. Sixty-two pathogenic APRT variants were identified, including six novel variants. Most common were the missense variants c.407T>C (p.(Met136Thr)) in Japan and c.194A>T (p.(Asp65Val)) in Iceland, as well as the splice-site variant c.400 + 2dup (p.(Ala108Glufs*3)) in the European population. Twenty-nine variants were detected in at least one of the six genomic databases. The highest cumulative minor allele frequency (cMAF) of pathogenic variants outside of Japan and Iceland was observed in the Irish population (0.2%), though no APRT deficiency cases have been reported in Ireland. The large number of cases in Japan and Iceland is consistent with a founder effect in these populations. There is no evidence for widespread underdiagnosis based on the current analysis. |
format |
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author |
Runolfsdottir, Hrafnhildur L. Sayer, John A. Indridason, Olafur S. Edvardsson, Vidar O. Jensson, Brynjar O. Arnadottir, Gudny A. Gudjonsson, Sigurjon A. Fridriksdottir, Run Katrinardottir, Hildigunnur Gudbjartsson, Daniel Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari Palsson, Runolfur |
author_facet |
Runolfsdottir, Hrafnhildur L. Sayer, John A. Indridason, Olafur S. Edvardsson, Vidar O. Jensson, Brynjar O. Arnadottir, Gudny A. Gudjonsson, Sigurjon A. Fridriksdottir, Run Katrinardottir, Hildigunnur Gudbjartsson, Daniel Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari Palsson, Runolfur |
author_sort |
Runolfsdottir, Hrafnhildur L. |
title |
Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency |
title_short |
Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency |
title_full |
Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency |
title_fullStr |
Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency |
title_full_unstemmed |
Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency |
title_sort |
allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency |
publisher |
Springer International Publishing |
publishDate |
2021 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298615/ http://www.ncbi.nlm.nih.gov/pubmed/33707627 https://doi.org/10.1038/s41431-020-00805-6 |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Eur J Hum Genet |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298615/ http://www.ncbi.nlm.nih.gov/pubmed/33707627 http://dx.doi.org/10.1038/s41431-020-00805-6 |
op_rights |
© The Author(s), under exclusive licence to European Society of Human Genetics 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
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CC-BY |
op_doi |
https://doi.org/10.1038/s41431-020-00805-6 |
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European Journal of Human Genetics |
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29 |
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7 |
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1061 |
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1070 |
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1766037385598992384 |