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<p>Since the establishment of molecular genetic methods in the diagnostics of hereditary diseases, autosomal dominant tubulointerstitial kidney diseases (ADTKD) have become established as a&#xa0;clearly defined and clinically relevant group of monogenic kidney diseases. Clinically, they typically present with slowly progressive chronic kidney disease accompanied by a&#xa0;largely unremarkable urinary sediment. The differential diagnostics of most ADTKD subtypes are comparatively straightforward due to additional gene-specific phenotypic features. In 2013 ADTKD-MUC1 (Mucin&#xa0;1) was described as an additional subtype that represents a&#xa0;particular diagnostic challenge. The clinical phenotype is largely restricted to the kidneys and pathogenic variants are located within a&#xa0;coding variable number tandem repeat (VNTR) region that cannot be reliably analyzed using established short-read sequencing technologies. More recently, bioinformatic approaches have been developed that enable the detection of signatures indicative of pathogenic MUC1-VNTR variants based on routinely generated short-read sequencing data. This enables a&#xa0;molecular genetic diagnosis of ADTKD-MUC1 in cases that would have remained unresolved using conventional analysis pipelines – both in ongoing diagnostic workflows and through retrospective reanalysis of previously completed cases. Consequently, a&#xa0;relevant diagnostic gap can be closed until long-read sequencing becomes broadly available in routine clinical diagnostics.</p>

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Autosomal-dominante tubulointerstielle Nierenerkrankung – Herausforderungen in der genetischen Diagnostik

  • 期刊论文

  • 发表日期：

    2026年7月29日

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  • Alexander Haas,
  • Matias Simons

摘要

Since the establishment of molecular genetic methods in the diagnostics of hereditary diseases, autosomal dominant tubulointerstitial kidney diseases (ADTKD) have become established as a clearly defined and clinically relevant group of monogenic kidney diseases. Clinically, they typically present with slowly progressive chronic kidney disease accompanied by a largely unremarkable urinary sediment. The differential diagnostics of most ADTKD subtypes are comparatively straightforward due to additional gene-specific phenotypic features. In 2013 ADTKD-MUC1 (Mucin 1) was described as an additional subtype that represents a particular diagnostic challenge. The clinical phenotype is largely restricted to the kidneys and pathogenic variants are located within a coding variable number tandem repeat (VNTR) region that cannot be reliably analyzed using established short-read sequencing technologies. More recently, bioinformatic approaches have been developed that enable the detection of signatures indicative of pathogenic MUC1-VNTR variants based on routinely generated short-read sequencing data. This enables a molecular genetic diagnosis of ADTKD-MUC1 in cases that would have remained unresolved using conventional analysis pipelines – both in ongoing diagnostic workflows and through retrospective reanalysis of previously completed cases. Consequently, a relevant diagnostic gap can be closed until long-read sequencing becomes broadly available in routine clinical diagnostics.