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

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.

Association of a novel homozygous mutation in the HMGCS2 gene with an HMGCSD in an Iranian patient

“…The SAMtools and ANNOVAR software packages were used for the identification and analysis of genetic variants, such as point mutations and indels. A 45 candidate gene was considered a variant that fulfilled the following criteria: 1: frameshift, nonsense, splice site variants, and missense; 2: absent or rare (frequency below 1%) in the two databases (dbSNP, 1000G); 3: homozygous variants in the patient (Heidari, Soleyman‐Nejad, et al, 2019; Heidari, Soleyman‐Nejad, Isazadeh, et al, 2020).…”