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Gene. 2018 May 31. pii: S0378-1119(18)30623-1. doi: 10.1016/j.gene.2018.05.112. [Epub ahead of print]

Mutational analysis in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD): Identification of five mutations in the PKD1 gene.

Author information

1
Laboratory of Human Molecular Genetics, Faculty of Medicine, Magida Boulila Street, 3029 Sfax, University of Sfax, Tunisia. Electronic address: abdelwahed.mayssa@yahoo.fr.
2
Center of Human Genetics, Institute of Pathology and Genetics, Biopark Charleroi Brussels South. Rue Adrienne Bolland 8. Aéropole de Gosselies, B - 6041 Gosselies, Belgium.
3
Nephrology and Hemodialyse department of Mohamed Ben Sassi Hospital, Route EbenKhaldoun, Mtorrech, Gabes 6014, Tunisia.
4
Nephrology Department of HediChaker Hospital, Route El Ain, Sfax 3089, Tunisia.
5
General Medicine department of Military Hospital, Route Mongi Slim, Gabes 6000, Tunisia.
6
Medical Genetics Department of HediChaker Hospital, Route El Ain, Sfax 3089, Tunisia.
7
Laboratory of Human Molecular Genetics, Faculty of Medicine, Magida Boulila Street, 3029 Sfax, University of Sfax, Tunisia.
8
Laboratory of Human Molecular Genetics, Faculty of Medicine, Magida Boulila Street, 3029 Sfax, University of Sfax, Tunisia; Medical Genetics Department of HediChaker Hospital, Route El Ain, Sfax 3089, Tunisia.

Abstract

Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most frequent genetic disorder of the kidneys, is characterized by a typical presenting symptoms include cysts development in different organs and a non-cysts manifestations. ADPKD is caused by mutations in PKD1 or PKD2 genes. In this study, we aimed to search for molecular causative defects among PKD1 and PKD2 genes. Eighteen patients were diagnosed based on renal ultrasonography and renal/extra-renal manifestations. Then, Sanger sequencing was performed for PKD1 and PKD2 genes. Multiplex Ligation dependent Probe Amplification method (MLPA) methods was performed for both PKD genes. Mutational analysis of the PKD2 gene revealed the absence of variants and no deletions or duplications of both PKD genes were detected. But three novels mutations i.e. p.S463C exon 7; c. c.11156+2T>C IVS38 and c.8161-1G>A IVS22 and two previously reported c.1522T>C exon 7 and c.412C>T exon 4 mutations in the PKD1 gene were detected. Bioinformatics tools predicted that the novel variants have a pathogenic effects on splicing machinery, pre-mRNA secondary structure and stability and protein stability. Our results highlighted molecular features of Tunisian patients with ADPKD and revealed novel variations that can be utilized in clinical diagnosis and in the evaluation of living kidney donor. To the best of our knowledge, this is the first report of Autosomal Polycystic Kidney Disease in Tunisia.

KEYWORDS:

Autosomal Dominant Polycystic Kidney Disease; Novel mutations; PKD1 gene, PKD2 gene; Splice variants

PMID:
29860066
DOI:
10.1016/j.gene.2018.05.112

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