Development and Validation of a Mass Spectrometry–Based Assay for the Molecular Diagnosis of Mucin-1 Kidney Disease
Author(s)Blumenstiel, Brendan; DeFelice, Matthew; Birsoy, Ozge; Bleyer, Anthony J.; Kmoch, Stanislav; Carter, Todd A.; Gnirke, Andreas; Kidd, Kendrah; Rehm, Heidi L.; Ronco, Lucienne; Gabriel, Stacey; Lennon, Niall J.; Lander, Eric Steven; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biology
The Journal of Molecular Diagnostics
Blumenstiel, Brendan et al. “Development and Validation of a Mass Spectrometry–Based Assay for the Molecular Diagnosis of Mucin-1 Kidney Disease.” The Journal of Molecular Diagnostics 18.4 (2016): 566–571. © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology
Final published version