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Article: The Value of Genetic Testing in Polycystic Kidney Diseases Illustrated by a Family With PKD2 and COL4A1 Mutations

TitleThe Value of Genetic Testing in Polycystic Kidney Diseases Illustrated by a Family With PKD2 and COL4A1 Mutations
Authors
KeywordsAutosomal dominant polycystic kidney disease (ADPKD)
case report
COL4A1
genetic testing
HANAC
pedigree
phenotypic variability
PKD2
targeted next-generation sequencing (TNGS)
Issue Date2018
Citation
American Journal of Kidney Diseases, 2018, v. 72, n. 2, p. 302-308 How to Cite?
AbstractThe diagnosis of autosomal dominant polycystic kidney disease (ADPKD) relies on imaging criteria in the setting of a positive familial history. Molecular analysis, seldom used in clinical practice, identifies a causative mutation in >90% of cases in the genes PKD1, PKD2, or rarely GANAB. We report the clinical and genetic dissection of a 7-generation pedigree, resulting in the diagnosis of 2 different cystic disorders. Using targeted next-generation sequencing of 65 candidate genes in a patient with an ADPKD-like phenotype who lacked the familial PKD2 mutation, we identified a COL4A1 mutation (p.Gln247*) and made the diagnosis of HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome. While 4 individuals had ADPKD-PKD2, various COL4A1-related phenotypes were identified in 5 patients, and 3 individuals with likely digenic PKD2/COL4A1 disease reached end-stage renal disease at around 50 years of age, significantly earlier than observed for either monogenic disorder. Thus, using targeted next-generation sequencing as part of the diagnostic approach in patients with cystic diseases provides differential diagnoses and identifies factors underlying disease variability. As specific therapies are rapidly developing for ADPKD, a precise etiologic diagnosis should be paramount for inclusion in therapeutic trials and optimal patient management.
Persistent Identifierhttp://hdl.handle.net/10722/316163
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.096
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCornec-Le Gall, Emilie-
dc.contributor.authorChebib, Fouad T.-
dc.contributor.authorMadsen, Charles D.-
dc.contributor.authorSenum, Sarah R.-
dc.contributor.authorHeyer, Christina M.-
dc.contributor.authorLanpher, Brendan C.-
dc.contributor.authorPatterson, Marc C.-
dc.contributor.authorAlbright, Robert C.-
dc.contributor.authorYu, Alan S.-
dc.contributor.authorTorres, Vicente E.-
dc.contributor.authorAbebe, Kaleab Z.-
dc.contributor.authorBae, Kyongtae T.-
dc.contributor.authorSchrier, Robert W.-
dc.contributor.authorChapman, Arlene B.-
dc.contributor.authorPerrone, Ronald D.-
dc.contributor.authorBraun, William E.-
dc.contributor.authorSteinman, Theodore I.-
dc.contributor.authorHarris, Peter C.-
dc.date.accessioned2022-08-24T15:49:27Z-
dc.date.available2022-08-24T15:49:27Z-
dc.date.issued2018-
dc.identifier.citationAmerican Journal of Kidney Diseases, 2018, v. 72, n. 2, p. 302-308-
dc.identifier.issn0272-6386-
dc.identifier.urihttp://hdl.handle.net/10722/316163-
dc.description.abstractThe diagnosis of autosomal dominant polycystic kidney disease (ADPKD) relies on imaging criteria in the setting of a positive familial history. Molecular analysis, seldom used in clinical practice, identifies a causative mutation in >90% of cases in the genes PKD1, PKD2, or rarely GANAB. We report the clinical and genetic dissection of a 7-generation pedigree, resulting in the diagnosis of 2 different cystic disorders. Using targeted next-generation sequencing of 65 candidate genes in a patient with an ADPKD-like phenotype who lacked the familial PKD2 mutation, we identified a COL4A1 mutation (p.Gln247*) and made the diagnosis of HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome. While 4 individuals had ADPKD-PKD2, various COL4A1-related phenotypes were identified in 5 patients, and 3 individuals with likely digenic PKD2/COL4A1 disease reached end-stage renal disease at around 50 years of age, significantly earlier than observed for either monogenic disorder. Thus, using targeted next-generation sequencing as part of the diagnostic approach in patients with cystic diseases provides differential diagnoses and identifies factors underlying disease variability. As specific therapies are rapidly developing for ADPKD, a precise etiologic diagnosis should be paramount for inclusion in therapeutic trials and optimal patient management.-
dc.languageeng-
dc.relation.ispartofAmerican Journal of Kidney Diseases-
dc.subjectAutosomal dominant polycystic kidney disease (ADPKD)-
dc.subjectcase report-
dc.subjectCOL4A1-
dc.subjectgenetic testing-
dc.subjectHANAC-
dc.subjectpedigree-
dc.subjectphenotypic variability-
dc.subjectPKD2-
dc.subjecttargeted next-generation sequencing (TNGS)-
dc.titleThe Value of Genetic Testing in Polycystic Kidney Diseases Illustrated by a Family With PKD2 and COL4A1 Mutations-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1053/j.ajkd.2017.11.015-
dc.identifier.pmid29395486-
dc.identifier.scopuseid_2-s2.0-85040971996-
dc.identifier.volume72-
dc.identifier.issue2-
dc.identifier.spage302-
dc.identifier.epage308-
dc.identifier.eissn1523-6838-
dc.identifier.isiWOS:000439368200020-
dc.identifier.f1000732605554-

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