Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency.

• Published in: European Journal of Human Genetics
• Main Authors: 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
• Other Authors: 1Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 2Internal Medicine and Rehabilitation Services, Landspitali-The National University Hospital, Reykjavik, Iceland. 3Renal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. 4Institute of Genetic Medicine, Newcastle University, Central Parkway Newcastle, Newcastle upon Tyne, UK. 5NIHR Biomedical Research Centre, Newcastle upon Tyne, UK. 6Children's Medical Center, Landspitali-The National University Hospital, Reykjavik, Iceland. 7deCODE genetics, Reykjavik, Iceland. 8School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland. 9Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. [e-mail]. 10Internal Medicine and Rehabilitation Services, Landspitali-The National University Hospital, Reykjavik, Iceland. [e-mail].
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Publishing Group 2021
• Subjects: Adenine Phosphoribosyltransferase; Iceland
• Online Access: http://hdl.handle.net/2336/621772; https://doi.org/10.1038/s41431-020-00805-6

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download 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. Rare Kidney Stone Consortium, a part of the National Center for Advancing Translational Sciences (NCATS) Rare ...