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.

Broad Institute of MIT and Harvard Cambridge Massachusetts

Broad Institute of MIT and Harvard Cambridge Massachusetts; Partners Healthcare Laboratory for Molecular Medicine Cambridge Massachusetts

Institute for Inherited Metabolic Disorders Charles University Prague Prague Czech Republic

Nephrology Section Wake Forest Baptist Medical Center Winston Salem North Carolina

References provided by Crossref.org

Eight-fold increased COVID-19 mortality in autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations: an observational study

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Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease

Autosomal dominant tubulointerstitial kidney disease: A review

The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project

Mitochondriopathy Manifesting as Inherited Tubulointerstitial Nephropathy Without Symptomatic Other Organ Involvement

Plasma Mucin-1 (CA15-3) Levels in Autosomal Dominant Tubulointerstitial Kidney Disease due to MUC1 Mutations

Outcomes of patient self-referral for the diagnosis of several rare inherited kidney diseases

Autosomal dominant tubulointerstitial kidney disease (ADTKD) in Ireland

Noninvasive Immunohistochemical Diagnosis and Novel MUC1 Mutations Causing Autosomal Dominant Tubulointerstitial Kidney Disease

Identification of a novel UMOD mutation (c.163G>A) in a Brazilian family with autosomal dominant tubulointerstitial kidney disease