Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency
Abstract 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...
Published in: | European Journal of Human Genetics |
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Online Access: | http://dx.doi.org/10.1038/s41431-020-00805-6 http://www.nature.com/articles/s41431-020-00805-6.pdf http://www.nature.com/articles/s41431-020-00805-6 |
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crspringernat:10.1038/s41431-020-00805-6 2023-05-15T16:47:33+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 Rare Kidney Stone Consortium Landspítali University Hospital Research Fund 2021 http://dx.doi.org/10.1038/s41431-020-00805-6 http://www.nature.com/articles/s41431-020-00805-6.pdf http://www.nature.com/articles/s41431-020-00805-6 en eng Springer Science and Business Media LLC https://creativecommons.org/licenses/by/4.0 https://creativecommons.org/licenses/by/4.0 CC-BY European Journal of Human Genetics volume 29, issue 7, page 1061-1070 ISSN 1018-4813 1476-5438 Genetics (clinical) Genetics journal-article 2021 crspringernat https://doi.org/10.1038/s41431-020-00805-6 2022-01-04T08:19:48Z Abstract 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. Article in Journal/Newspaper Iceland Springer Nature (via Crossref) European Journal of Human Genetics |
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Open Polar |
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Springer Nature (via Crossref) |
op_collection_id |
crspringernat |
language |
English |
topic |
Genetics (clinical) Genetics |
spellingShingle |
Genetics (clinical) Genetics 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 |
topic_facet |
Genetics (clinical) Genetics |
description |
Abstract 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. |
author2 |
Rare Kidney Stone Consortium Landspítali University Hospital Research Fund |
format |
Article in Journal/Newspaper |
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 Science and Business Media LLC |
publishDate |
2021 |
url |
http://dx.doi.org/10.1038/s41431-020-00805-6 http://www.nature.com/articles/s41431-020-00805-6.pdf http://www.nature.com/articles/s41431-020-00805-6 |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
European Journal of Human Genetics volume 29, issue 7, page 1061-1070 ISSN 1018-4813 1476-5438 |
op_rights |
https://creativecommons.org/licenses/by/4.0 https://creativecommons.org/licenses/by/4.0 |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.1038/s41431-020-00805-6 |
container_title |
European Journal of Human Genetics |
_version_ |
1766037644499746816 |