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J Mol Diagn DOI:10.1016/j.jmoldx.2016.03.003

Development and Validation of a Mass Spectrometry-Based Assay for the Molecular Diagnosis of Mucin-1 Kidney Disease.

Publication TypeJournal Article
Year of Publication2016
AuthorsBlumenstiel, B, DeFelice, M, Birsoy, O, Bleyer, AJ, Kmoch, S, Carter, TA, Gnirke, A, Kidd, K, Rehm, HL, Ronco, L, Lander, ES, Gabriel, S, Lennon, NJ
JournalJ Mol Diagn
Date Published2016 Jul

Mucin-1 kidney disease, previously described as medullary cystic kidney disease type 1 (MCKD1, OMIM 174000), is an autosomal dominant tubulointerstitial kidney disease recently shown to be caused by a single-base insertion within the variable number tandem repeat region of the MUC1 gene. Because of variable age of disease onset and often subtle signs and symptoms, clinical diagnosis of mucin-1 kidney disease and differentiation from other forms of hereditary kidney disease have been difficult. The causal insertion resides in a variable number tandem repeat region with high GC content, which has made detection by standard next-generation sequencing impossible to date. The inherently difficult nature of this mutation required an alternative method for routine detection and clinical diagnosis of the disease. We therefore developed and validated a mass spectrometry-based probe extension assay with a series of internal controls to detect the insertion event using 24 previously characterized positive samples from patients with mucin-1 kidney disease and 24 control samples known to be wild type for the variant. Validation results indicate an accurate and reliable test for clinically establishing the molecular diagnosis of mucin-1 kidney disease with 100% sensitivity and specificity across 275 tests called.


Alternate JournalJ Mol Diagn
PubMed ID27157321
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