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dc.contributor.authorAstuti, D
dc.contributor.authorSabir, A
dc.contributor.authorFulton, P
dc.contributor.authorZatyka, M
dc.contributor.authorWilliams, D
dc.contributor.authorHardy, C
dc.contributor.authorMilan, G
dc.contributor.authorFavaretto, F
dc.contributor.authorYu-Wai-Man, P
dc.contributor.authorRohayem, J
dc.contributor.authorLopez de Heredia, M
dc.contributor.authorHershey, T
dc.contributor.authorTranebjaerg, L
dc.contributor.authorChen, J-H
dc.contributor.authorChaussenot, A
dc.contributor.authorNunes, V
dc.contributor.authorMarshall, B
dc.contributor.authorMcAfferty, S
dc.contributor.authorTillmann, V
dc.contributor.authorMaffei, P
dc.contributor.authorPaquis-Flucklinger, V
dc.contributor.authorGeberhiwot, T
dc.contributor.authorMlynarski, W
dc.contributor.authorParkinson, K
dc.contributor.authorPicard, V
dc.contributor.authorEsteban Bueno, G
dc.contributor.authorDias, R
dc.contributor.authorArnold, A
dc.contributor.authorRichens, C
dc.contributor.authorPaisey, R
dc.contributor.authorUrano, F
dc.contributor.authorSemple, R
dc.contributor.authorSinnott, R
dc.contributor.authorBarrett, TG
dc.date.accessioned2021-02-04T00:43:41Z
dc.date.available2021-02-04T00:43:41Z
dc.date.issued2017-07-01
dc.identifier.citationAstuti, D., Sabir, A., Fulton, P., Zatyka, M., Williams, D., Hardy, C., Milan, G., Favaretto, F., Yu-Wai-Man, P., Rohayem, J., Lopez de Heredia, M., Hershey, T., Tranebjaerg, L., Chen, J. -H., Chaussenot, A., Nunes, V., Marshall, B., McAfferty, S., Tillmann, V. ,... Barrett, T. G. (2017). Monogenic diabetes syndromes: Locus-specific databases for Alstrom, Wolfram, and Thiamine-responsive megaloblastic anemia. HUMAN MUTATION, 38 (7), pp.764-777. https://doi.org/10.1002/humu.23233.
dc.identifier.issn1059-7794
dc.identifier.urihttp://hdl.handle.net/11343/259176
dc.description.abstractWe developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström, and Thiamine-responsive megaloblastic anemia syndromes, respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1. We then investigated genotype-phenotype relations for the WFS1 gene. The presence of biallelic loss-of-function variants predicted Wolfram syndrome defined by insulin-dependent diabetes and optic atrophy, with a sensitivity of 79% (95% CI 75%-83%) and specificity of 92% (83%-97%). The presence of minor loss-of-function variants in WFS1 predicted isolated diabetes, isolated deafness, or isolated congenital cataracts without development of the full syndrome (sensitivity 100% [93%-100%]; specificity 78% [73%-82%]). The ability to provide a prognostic prediction based on genotype will lead to improvements in patient care and counseling. The development of the database as a repository for monogenic diabetes gene variants will allow prognostic predictions for other diabetes syndromes as next-generation sequencing expands the repertoire of genotypes and phenotypes. The database is publicly available online at https://lovd.euro-wabb.org.
dc.languageEnglish
dc.publisherWILEY
dc.titleMonogenic diabetes syndromes: Locus-specific databases for Alstrom, Wolfram, and Thiamine-responsive megaloblastic anemia
dc.typeJournal Article
dc.identifier.doi10.1002/humu.23233
melbourne.affiliation.departmentComputing and Information Systems
melbourne.affiliation.facultyEngineering and Information Technology
melbourne.source.titleHuman Mutation
melbourne.source.volume38
melbourne.source.issue7
melbourne.source.pages764-777
dc.rights.licenseCC BY
melbourne.elementsid1205294
melbourne.contributor.authorSinnott, Richard
dc.identifier.eissn1098-1004
melbourne.accessrightsOpen Access


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