Identification of PKHD1 multiexon deletions using multiplex ligation-dependent probe amplification and quantitative polymerase chain reaction.

Introduction: Mutations in the PKHD1 gene are responsible for autosomal recessive polycystic kidney disease (ARPKD). Using exon scanning by denaturing high-performance liquid chromatography (dHPLC) or bidirectional sequencing of all exons constituting the longest open reading frame, the mutation detection rate reaches ∼82% and minor lesion mutations include truncating, splice, and missense mutations. Aim: The main aim of this study was to screen ARPKD patients in whom only one pathogenic PKHD1 mutation was identified after bidirectional sequencing of the longest open reading frame, for gene copy number alterations by employing multiplex ligation-dependent probe amplification complemented with quantitative real-time polymerase chain reaction. Results: Sixteen ARPKD probands were studied in whom only one clearly pathogenic mutation was previously identified. One patient with a suspected homozygous deletion of the exons 1–37 was also included in this cohort. Three distinct PKHD1 germ-line deletions were iden...