Noninvasive Immunohistochemical Diagnosis and Novel Mutations Causing Autosomal Dominant Tubulointerstitial Kidney Disease.

J Am Soc Nephrol
Authors
Keywords
Abstract

BACKGROUND: Autosomal dominant tubulointerstitial kidney disease caused by mucin-1 gene () mutations (ADTKD-) is characterized by progressive kidney failure. Genetic evaluation for ADTKD- 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 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-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 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 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-.

Year of Publication
2018
Journal
J Am Soc Nephrol
Volume
29
Issue
9
Pages
2418-2431
Date Published
2018 09
ISSN
1533-3450
DOI
10.1681/ASN.2018020180
PubMed ID
29967284
PubMed Central ID
PMC6115665
Links
Grant list
R21 DK106584 / DK / NIDDK NIH HHS / United States