1 Genesis Genoma Lab, Genetic Diagnosis, Clinical Genetics & Research, Athens, Greece.

2 Neonatal Intensive Care Unit, 2nd Department of Pediatrics, Athens University Medical School, 'P. & A. Kyriakou' Children’s Hospital of Athens, Athens, Greece.


Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the PKHD1gene. In the present study, we describe a severe case of ARPKD carrying a point mutation and a novel four-exon deletion of PKHD1 gene.
Materials and Methods
The PKHD1, PKD1 and PKD2 genes were analyzed using next-generation sequencing, whereas the PKHD1 gene exon deletions/duplications were screened using multiplex ligation-dependent probe amplification.
The c.2279G>A (p.Arg760His) mutation and a deletion encompassing exons 24-27 of PKHD1 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.
Given that the molecular analysis of ARPKD is mainly based on sequencing techniques, the PKHD1 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.