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Identification of Three Novel Frameshift Mutations in the PKD1 Gene in Iranian Families with Autosomal Dominant Polycystic Kidney Disease Using Efficient Targeted Next-Generation Sequencing

Authors :
Fariba Ranjzad
Nasser Aghdami
Ahmad Tara
Marzieh Mohseni
Reza Moghadasali
Abbas Basiri
Source :
Kidney & Blood Pressure Research, Vol 43, Iss 2, Pp 471-478 (2018)
Publication Year :
2018
Publisher :
Karger Publishers, 2018.

Abstract

Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited cystic kidney diseases caused by mutations in two large multi-exon genes, PKD1 and PKD2. High allelic heterogeneity and duplication of PKD1 exons 1–32 as six pseudo genes on chromosome 16 complicate molecular analysis of this disease. Methods: We applied targeted next-generation sequencing (NGS) in 9 non-consanguineous unrelated Iranian families with ADPKD to identify the genes hosting disease-causing mutations. This approach was confirmed by Sanger sequencing. Results: Here, we determined three different novel frameshift mutations and four previously reported nonsense mutations in the PKD1 gene encoding polycystin1 in heterozygotes. Conclusion: This study demonstrates the effectiveness of NGS in significantly reducing the cost and time for simultaneous sequence analysis of PKD1 and PKD2, simplifying the genetic diagnostics of ADPKD. Although a probable correlation between the mutation types and phenotypic outcome is possible, however for more extensive studies in future, the consideration of renal hypouricemia (RHUC) and PKD1 coexistence may be helpful. The novel frameshift mutations reported by this study are p. Q1997X, P. D73X and p. V336X.

Details

Language :
English
ISSN :
14204096 and 14230143
Volume :
43
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Kidney & Blood Pressure Research
Publication Type :
Academic Journal
Accession number :
edsdoj.70d27d01833f458bbe4a79302d03f949
Document Type :
article
Full Text :
https://doi.org/10.1159/000488471