Application of whole exome sequence analysis for diagnosing familial nephropathy and selecting living donor for renal transplantation

Abstract

【Objective】 This paper investigates the incidence and genetic analysis of hereditary kidney diseases in adult patients, focusing on autosomal dominant tubulointerstitial kidney disease (ADTKD) and focal segmental glomerulosclerosis (FSGS) due to genetic mutations such as MUC1 and LAMA5. It aims to highlight the need to recognize atypical presentations of hereditary kidney diseases in adults and the importance of genetic testing in diagnosis and treatment planning.

【Methods】 The study utilized Whole Exome Sequencing (WES) to analyze patients with hereditary kidney diseases. This method selectively reads the exons of human genes to identify genetic mutations, particularly focusing on rare pathogenic variants. Analysis involved increasing the study cohort and comparing genetic expressions, such as those in podocytes, using single-cell data for accurate diagnosis.

【Results】 In the study, ADTKD was linked to mutations in genes like UMOD and MUC1. The research identified a Japanese family with a unique MUC1 mutation presenting with both kidney dysfunction and interstitial pneumonia. In terms of FSGS, the study documented the first global case of an LAMA5 gene heterozygous mutation causing progressive kidney dysfunction alongside lung structural changes. These findings highlight the variability and complexity of adult hereditary kidney diseases’ presentations.

【Conclusion】 The novel genetic mutations identified in MUC1 and LAMA5 not only emphasize the varying geographical prevalence of genetic diseases but also demonstrate the extensive systemic manifestations associated with these mutations. It is essential to remain vigilant for atypical presentations in adult hereditary kidney diseases, emphasizing the critical role of comprehensive genetic analysis in clinical practice to guide diagnosis and management.