Identification of a pathogenic mutation in a Chinese pedigree with polycystic kidney disease

Area of Science:

• Genetics and Molecular Biology
• Nephrology
• Inherited Diseases

Background:

• Polycystic kidney disease (PKD) is a severe inherited disorder affecting 1 in 500–1,000 individuals globally.
• The disease is characterized by the development of numerous cysts in both kidneys, leading to structural damage and impaired kidney function.
• Autosomal dominant PKD (ADPKD) is the most common inherited kidney disease, primarily caused by mutations in the PKD1 gene.

Purpose of the Study:

• To identify the genetic cause of PKD in a consanguineous family.
• To characterize novel variants within the PKD1 gene.
• To investigate the pathogenic role of identified variants in ADPKD.

Main Methods:

• Whole exome sequencing was performed on the proband to identify potential causative genes.
• Candidate gene segments were amplified using nested polymerase chain reaction.
• Sanger sequencing was employed for precise variant detection and confirmation.

Main Results:

• A novel duplication variant (NM_001009944.2:c.9359dupA:p.Y3120_E3121delinsX) was identified in the PKD1 gene.
• A missense mutation (c.G9022A:p.V3008M) was also detected in the PKD1 gene.
• The duplication variant, located in the polycystin-1, lipoxygenase, alpha-toxin domain, was confirmed as the pathogenic factor for ADPKD in this family.

Conclusions:

• The identified duplication variant in PKD1 is the pathogenic cause of autosomal dominant PKD in the studied family.
• Genetic analysis of PKD1 variants, including those in specific domains like the N-terminal region, is crucial for understanding ADPKD.
• This study contributes to the genetic diagnosis and understanding of ADPKD, highlighting the importance of novel variant identification.