|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Blumenstiel, 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|
|Journal||J Mol Diagn|
|Date Published||2016 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 Journal||J Mol Diagn|