Zivna, Martina, Kidd, Kendrah, Pristoupilova, Anna ORCID: 0000-0003-0047-9405, Baresova, Veronika, DeFelice, Mathew, Blumenstiel, Brendan, Harden, Maegan, Conlon, Peter, Lavin, Peter, Connaughton, Dervla M., Hartmannova, Hana, Hodanova, Katerina, Stranecky, Viktor ORCID: 0000-0002-2599-6479, Vrbacka, Alena, Vylet'al, Petr, Zivny, Jan, Votruba, Miroslav, Sovova, Jana, Hulkova, Helena, Robins, Victoria, Perry, Rebecca, Wenzel, Andrea, Beck, Bodo B., Seeman, Tomas, Viklicky, Ondrej ORCID: 0000-0003-1049-2195, Rajnochova-Bloudickova, Sylvie, Papagregoriou, Gregory, Deltas, Constantinos C., Alper, Seth L., Greka, Anna, Bleyer, Anthony J. and Kmoch, Stanislav (2018). Noninvasive Immunohistochemical Diagnosis and Novel MUC1 Mutations Causing Autosomal Dominant Tubulointerstitial Kidney Disease. J. Am. Soc. Nephrol., 29 (9). S. 2418 - 2432. WASHINGTON: AMER SOC NEPHROLOGY. ISSN 1533-3450

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Abstract

Background Autosomal dominant tubulointerstitial kidney disease caused by mucin-1 gene (MUC1) mutations (ADTKD-MUC1) is characterized by progressive kidney failure. Genetic evaluation for ADTKD-MUC1 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 MUC1 mutations in individuals with positive immunohistochemical staining for the MUC1fs protein. Methods We performed MUC1fs immunostaining on urinary cell smears and various tissues from ADTKD-MUC1-positive and -negative 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 MUC1 frameshift mutations. Results 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 MUC1 frameshift mutations that all predict production of the identical MUC1fs protein. Conclusions 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-MUC1.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zivna, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kidd, KendrahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pristoupilova, AnnaUNSPECIFIEDorcid.org/0000-0003-0047-9405UNSPECIFIED
Baresova, VeronikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
DeFelice, MathewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blumenstiel, BrendanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harden, MaeganUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Conlon, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lavin, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Connaughton, Dervla M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmannova, HanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hodanova, KaterinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stranecky, ViktorUNSPECIFIEDorcid.org/0000-0002-2599-6479UNSPECIFIED
Vrbacka, AlenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vylet'al, PetrUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zivny, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Votruba, MiroslavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sovova, JanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hulkova, HelenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robins, VictoriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perry, RebeccaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wenzel, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beck, Bodo B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seeman, TomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Viklicky, OndrejUNSPECIFIEDorcid.org/0000-0003-1049-2195UNSPECIFIED
Rajnochova-Bloudickova, SylvieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Papagregoriou, GregoryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deltas, Constantinos C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alper, Seth L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greka, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bleyer, Anthony J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kmoch, StanislavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-174096
DOI: 10.1681/ASN.2018020180
Journal or Publication Title: J. Am. Soc. Nephrol.
Volume: 29
Number: 9
Page Range: S. 2418 - 2432
Date: 2018
Publisher: AMER SOC NEPHROLOGY
Place of Publication: WASHINGTON
ISSN: 1533-3450
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CYTOSINE INSERTION; GENE; FAMILY; FEATURES; ANEMIA; TYPE-1; VNTRMultiple languages
Urology & NephrologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17409

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