Identification of a Novel Intragenic Deletion of the PHKD1 Gene in a Patient with Autosomal Recessive Polycystic Kidney Disease

Abstract

<strong><em>Background</em></strong><br /> Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the <em>PKHD1</em>gene. In the present study, we describe a severe case of ARPKD carrying a point mutation and a novel four-exon deletion of <em>PKHD1</em> gene.<br /> <strong><em>Materials and Methods</em></strong><br /> The <em>PKHD1</em>, <em>PKD1 </em>and<em> PKD2 </em>genes were analyzed using next-generation sequencing, whereas the <em>PKHD1</em> gene exon deletions/duplications were screened using multiplex ligation-dependent probe amplification.<br /> <strong><em>Results</em></strong><br /> The c.2279G>A (p.Arg760His) mutation and a deletion encompassing exons 24-27 of <em>PKHD1</em> gene were detected in compound heterozygosity in the affected neonate. The complete documentation of the genetic basis of the disease offered the possibility of a targeted prenatal diagnosis in the following pregnancy of the couple.<br /> <strong><em>Conclusion</em></strong><br /> Given that the molecular analysis of ARPKD is mainly based on sequencing techniques, the <em>PKHD1</em> gene exon deletion/duplication screening should be performed as a complementary assay in patients suspected to have ARPKD in the absence of two pathogenic mutations.