Identification of Two Novel Mutations in Gene from Two Families with Polycystic Kidney Disease by Whole Exome Sequencing.

Background: Polycystic kidney disease (PKD) is an autosomal recessive disorder resulting from mutations in the gene on chromosome 6 (6p12), a large gene spanning 470 kb of genomic DNA.

Objective: The aim of the present study was to report newly identified mutations in the 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 study.

Results: In the 3 month-old boy, a novel homozygous frameshift mutation was detected in the gene, which can cause PKD. Moreover, we identified three novel heterozygous missense mutations in , , and 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 gene and a novel mutation in gene.

Conclusion: In general, we have identified two novel mutations in the 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.