{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:01:49Z","timestamp":1790737309022,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,9]]},"abstract":"\n Background<\/jats:title>\n \n Providing the correct diagnosis for patients with tubulointerstitial kidney disease and secondary degenerative disorders, such as hypertension, remains a challenge. The autosomal dominant tubulointerstitial kidney disease (ADTKD) subtype caused by\n MUC1<\/jats:italic>\n mutations (ADTKD-\n MUC1<\/jats:italic>\n ) is particularly difficult to diagnose, because the mutational hotspot is a complex repeat domain, inaccessible with routine sequencing techniques. Here, we further evaluated SNaPshot minisequencing as a technique for diagnosing ADTKD-\n MUC1<\/jats:italic>\n and assessed immunodetection of the disease-associated mucin 1 frameshift protein (MUC1-fs) as a nongenetic technique.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We re-evaluated detection of\n MUC1<\/jats:italic>\n mutations by targeted repeat enrichment and SNaPshot minisequencing by haplotype reconstruction\n via<\/jats:italic>\n microsatellite analysis in three independent ADTKD-\n MUC1<\/jats:italic>\n families. Additionally, we generated rabbit polyclonal antibodies against MUC1-fs and evaluated immunodetection of wild-type and mutated allele products in human kidney biopsy specimens.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The detection of\n MUC1<\/jats:italic>\n mutations by SNaPshot minisequencing was robust. Immunostaining with our MUC1-fs antibodies and an MUC1 antibody showed that both proteins are readily detectable in human ADTKD-\n MUC1<\/jats:italic>\n kidneys, with mucin 1 localized to the apical membrane and MUC1-fs abundantly distributed throughout the cytoplasm. Notably, immunohistochemical analysis of MUC1-fs expression in clinical kidney samples facilitated reliable prediction of the disease status of individual patients.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Diagnosing ADTKD-\n MUC1<\/jats:italic>\n by molecular genetics is possible, but it is technically demanding and labor intensive. However, immunohistochemistry on kidney biopsy specimens is feasible for nongenetic diagnosis of ADTKD-\n MUC1<\/jats:italic>\n and therefore, a valid method to select families for further diagnostics. Our data are compatible with the hypothesis that specific molecular effects of MUC1-fs underlie the pathogenesis of this disease.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2018030245","type":"journal-article","created":{"date-parts":[[2018,7,26]],"date-time":"2018-07-26T09:29:36Z","timestamp":1532597376000},"page":"2298-2309","source":"Crossref","is-referenced-by-count":42,"title":["Biallelic Expression of Mucin-1 in Autosomal Dominant Tubulointerstitial Kidney Disease: Implications for Nongenetic Disease Recognition"],"prefix":"10.1681","volume":"29","author":[{"given":"Karl X.","family":"Knaup","sequence":"first","affiliation":[{"name":"Department of Nephrology and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hackenbeck","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernt","family":"Popp","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Stoeckert","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"B\u00fcttner-Herold","sequence":"additional","affiliation":[{"name":"Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Pfister","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schueler","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didem","family":"Seven","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, and"},{"name":"Cerrahpa\u015fa Medical Faculty, Department of Medical Biology, Istanbul University, Istanbul, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette M.","family":"May","sequence":"additional","affiliation":[{"name":"Institute for Surgical Pathology, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Halbritter","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Leipzig, Leipzig, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann-Josef","family":"Gr\u00f6ne","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Pathology, Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6301-6363","authenticated-orcid":false,"given":"Andr\u00e9","family":"Reis","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodo B.","family":"Beck","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Amann","sequence":"additional","affiliation":[{"name":"Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif B.","family":"Ekici","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Wiesener","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,7,26]]},"reference":[{"key":"B1-20230829","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1159\/000088491","article-title":"Population-based screening for family history of end-stage renal disease among incident 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