Background: Polycystic kidney disease (PKD) is an autosomal recessive disorder resulting
from mutations in the PKHD1 gene on chromosome 6 (6p12), a large gene spanning 470 kb of
Objective: The aim of the present study was to report newly identified mutations in the PKHD1
gene in two Iranian families with PKD.
Materials and Methods: Genetic alterations of a 3-month-old boy and a 27-year-old girl with PKD
were evaluated using whole-exome sequencing. The PCR direct sequencing was performed to analyse
the co-segregation of the variants with the disease in the family. Finally, the molecular function
of the identified novel mutations was evaluated by in silico study.
Results: In the 3 month-old boy, a novel homozygous frameshift mutation was detected in the
PKHD1 gene, which can cause PKD. Moreover, we identified three novel heterozygous missense
mutations in ATIC, VPS13B, and TP53RK genes. In the 27-year-old woman, with two recurrent
abortions history and two infant mortalities at early weeks due to metabolic and/or renal disease,
we detected a novel missense mutation on PKHD1 gene and a novel mutation in ETFDH gene.
Conclusion: In general, we have identified two novel mutations in the PKHD1 gene. These molecular
findings can help accurately correlate genotype and phenotype in families with such disease in
order to reduce patient births through preoperative genetic diagnosis or better management of disorders.