Molecular Genetic Analysis of PKHD1 Mutations in Pedigrees With Autosomal Recessive Polycystic Kidney Disease

Area of Science:

• Genetics
• Molecular Biology
• Pediatric Nephrology

Background:

• Autosomal recessive polycystic kidney disease (ARPKD) is a severe genetic disorder affecting kidney and liver development.
• The PKHD1 gene, encoding fibrocystin/polyductin, is crucial for kidney development and function.
• Mutations in PKHD1 are the primary cause of ARPKD, leading to characteristic collecting duct dilation and congenital hepatic fibrosis.

Purpose of the Study:

• To investigate the spectrum of PKHD1 mutations in Iranian families with autosomal recessive polycystic kidney disease (ARPKD).
• To identify novel and known mutations within the PKHD1 gene associated with ARPKD.
• To understand the genetic basis of ARPKD in a population with a high rate of consanguineous marriages.

Main Methods:

• Mutational analysis of the PKHD1 gene was conducted in 11 families affected by ARPKD.
• Next-Generation Sequencing (NGS) and Sanger sequencing techniques were employed for comprehensive genetic analysis.
• Affected individuals included fetuses and infants who either were aborted or died shortly after birth.

Main Results:

• Seven mutations in the PKHD1 gene were identified across the 11 families.
• Four novel mutations (c.6469C>T, c.9218 G>A, c.10456T>C, and c.8863C>G) were discovered.
• Three previously reported mutations (c.9524A>G, c.1095G>A, c.1123C>T) were also identified.

Conclusions:

• The study identified a range of PKHD1 mutations, contributing to the understanding of ARPKD genetics.
• The findings underscore the critical role of the PKHD1 gene in the pathogenesis of ARPKD.
• Given the high frequency of consanguineous marriages in Iran, a higher prevalence of ARPKD is anticipated compared to global averages.