Algorithm for efficient PKHD1 mutation screening in autosomal recessive polycystic kidney disease (ARPKD)

Hum Mutat. 2005 Mar;25(3):225-31. doi: 10.1002/humu.20145.


Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of childhood renal- and liver-related morbidity and mortality with variable disease expression. While most cases manifest peri-/neonatally with a high mortality rate in the first month of life, others survive to adulthood. ARPKD is caused by mutations in the Polycystic Kidney and Hepatic Disease 1 (PKHD1) gene on chromosome 6p12. PKHD1 is an exceptionally large gene (470 kb) with a longest open reading frame transcript of 67 exons predicted to encode a 4,074-amino acid (aa) (447 kDa) multidomain integral membrane protein (fibrocystin/polyductin) of unknown function. Recent DHPLC-based mutational studies have reported detection rates of about 80% and a minimum of one PKHD1 mutation in more than 95% of families. Thus far, a total of 263 different PKHD1 mutations (639 mutated alleles) are included in the locus-specific database ( Except for a few population-specific founder alleles and the common c.107C>T (p.Thr36Met) missense change, PKHD1 is characterized by significant allelic diversity, making mutation screening time-consuming and labor-intensive. Mutations are distributed throughout the gene's coding sequence; however, they are not equally scattered. Thus, we aimed to set up an algorithm for efficient molecular genetic diagnostics in ARPKD. A total of 80% of known PKHD1 mutations can be identified if a subset of 27 out of 77 DHPLC fragments is screened. The current study provides an essential platform for PKHD1 mutation screening in a routine setting that will largely alleviate molecular genetic diagnostics in patients suspected to have ARPKD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Algorithms
  • Alleles
  • Chromatography, High Pressure Liquid
  • Cohort Studies
  • DNA Mutational Analysis / methods*
  • Databases, Factual
  • Genes, Recessive
  • Genetic Testing / methods*
  • Haplotypes / genetics
  • Humans
  • Open Reading Frames / genetics
  • Polycystic Kidney, Autosomal Recessive / genetics*
  • Receptors, Cell Surface / genetics*
  • Sensitivity and Specificity
  • White People / genetics


  • PKHD1 protein, human
  • Receptors, Cell Surface