Identification of Two Novel Mutations in PKHD1 Gene from Two Families with Polycystic Kidney Disease by Whole Exome Sequencing

Author(s): Masoud Heidari, Hamid Gharshasbi, Alireza Isazadeh, Morteza Soleyman-Nejad, Mohammad Hossein Taskhiri, Javad Shapouri, Manzar Bolhassani, Nahid Sadighi, Mansour Heidari*

Journal Name: Current Genomics

Volume 22 , Issue 3 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


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 genomic DNA.

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.

Keywords: Polycystic kidney disease, PKHD1 gene, whole-exome sequencing, mutation, disorder, ETFDH gene.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 18 February, 2021
Page: [232 - 236]
Pages: 5
DOI: 10.2174/1389202922666210219111810
Price: $65

Article Metrics

PDF: 208