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

[ Vol. 22 , Issue. 3 ]


Masoud Heidari , Hamid Gharshasbi, Alireza Isazadeh, Morteza Soleyman-Nejad, Mohammad Hossein Taskhiri, Javad Shapouri, Manzar Bolhassani, Nahid Sadighi and Mansour Heidari*   Pages 232 - 236 ( 5 )


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.


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


Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Department of Genetics, Tabriz Branch Islamic Azad University, Tabriz, Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Ariagene Medical Genetics Laboratory, Qom, Ariagene Medical Genetics Laboratory, Qom, Pediatric Clinical Research and Development Center, Qom University of Medical Sciences, Qom, Ariagene Medical Genetics Laboratory, Qom, Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences (TUMS), Tehran, Department of Medical Genetics, Tehran University of Medical Sciences (TUMS), Tehran

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