{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:01:04Z","timestamp":1790737264385,"version":"4.1.0"},"reference-count":21,"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 Autosomal dominant tubulointerstitial kidney disease caused by mucin-1 gene (\n MUC1<\/jats:italic>\n ) mutations (ADTKD-\n MUC1<\/jats:italic>\n ) is characterized by progressive kidney failure. Genetic evaluation for ADTKD-\n MUC1<\/jats:italic>\n specifically tests for a cytosine duplication that creates a unique frameshift protein (MUC1fs). Our goal was to develop immunohistochemical methods to detect the MUC1fs created by the cytosine duplication and, possibly, by other similar frameshift mutations and to identify novel\n MUC1<\/jats:italic>\n mutations in individuals with positive immunohistochemical staining for the MUC1fs protein.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We performed MUC1fs immunostaining on urinary cell smears and various tissues from ADTKD-\n MUC1\u2013<\/jats:italic>\n positive and \u2013negative controls as well as in individuals from 37 ADTKD families that were negative for mutations in known ADTKD genes. We used novel analytic methods to identify\n MUC1<\/jats:italic>\n frameshift mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n After technique refinement, the sensitivity and specificity for MUC1fs immunostaining of urinary cell smears were 94.2% and 88.6%, respectively. Further genetic testing on 17 families with positive MUC1fs immunostaining revealed six families with five novel\n MUC1<\/jats:italic>\n frameshift mutations that all predict production of the identical MUC1fs protein.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We developed a noninvasive immunohistochemical method to detect MUC1fs that, after further validation, may be useful in the future for diagnostic testing. Production of the MUC1fs protein may be central to the pathogenesis of ADTKD-\n MUC1<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2018020180","type":"journal-article","created":{"date-parts":[[2018,7,2]],"date-time":"2018-07-02T10:55:20Z","timestamp":1530528920000},"page":"2418-2431","source":"Crossref","is-referenced-by-count":61,"title":["Noninvasive Immunohistochemical Diagnosis and Novel MUC1 Mutations Causing Autosomal Dominant Tubulointerstitial Kidney Disease"],"prefix":"10.1681","volume":"29","author":[{"given":"Martina","family":"\u017divn\u00e1","sequence":"first","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendrah","family":"Kidd","sequence":"additional","affiliation":[{"name":"Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North 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Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maegan","family":"Harden","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-9531","authenticated-orcid":false,"given":"Peter","family":"Conlon","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland;"},{"name":"Royal College of Surgeons, Dublin, Ireland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lavin","sequence":"additional","affiliation":[{"name":"Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dervla M.","family":"Connaughton","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland;"},{"name":"Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Hartmannov\u00e1","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate\u0159ina","family":"Hoda\u0148ov\u00e1","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Str\u00e1neck\u00fd","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Vrback\u00e1","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Vyle\u0165al","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"\u017divn\u00fd","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, First Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Votruba","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Sovov\u00e1","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"H\u016flkov\u00e1","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine,"},{"name":"Institute of Pathology, First Faculty of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Robins","sequence":"additional","affiliation":[{"name":"Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Perry","sequence":"additional","affiliation":[{"name":"Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany;"},{"name":"Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodo B.","family":"Beck","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany;"},{"name":"Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Seeman","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Second Faculty of Medicine, Charles University, Prague, Czech 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Sciences, University of Cyprus, Nicosia, Cyprus;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth L.","family":"Alper","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Vascular Biology Research Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Greka","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts;"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts; and"},{"name":"Department of Medicine, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Bleyer","sequence":"additional","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine,"},{"name":"Section on 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