Mutationsanalyse der Exone 26 bis 52 des PKHD1-Gens bei der Autosomal Rezessiv erblichen Polyzystischen Nierenerkrankung (ARPKD)

Autosomal recessive polycystic kidney disease (ARPKD) is a severe inherited disorder with a proposed incidence of 1/20.000 live births. In 1994 the ARPKD gene was mapped to chromosome 6p21-cen. Two independent groups unraveled the PKHD1 gene in 2002. This study reports mutation screening by SSCP analysis of the exons 26-52 of the longest continuous open reading frame of the PKHD1 gene in 90 ARPKD families. It identifies 11 different mutations, 9 of them have not been reported previously. Of the observed changes, 2 were deletions/insertions und 7 were missense mutations. In addition to the reported mutations, 18 polymorphisms were observed; 14 of them have not been reported previously. The results of this study combined with the results of other mutation analysis of the exons 2-25 and 53-67 (Bergmann et al. 2003) make up a detection rate of 61% (2 underlying mutations were disclosed in 40 individuals (45%), 1 mutation in 30 cases (33%), no mutation could be found in 20 patients (22%)). In patients in whom only one or no mutation was found, it is likely that limitations of SSCP technique hampered detection of the second or any variant (gross deletions or genomic rearrangements are not detectable by SSCP). Preliminary genotype-phenotype correlations could be established for the type of mutation. The proportion of chain-terminating mutations was significantly higher in the severe group than in the moderately affected cohort. Survival past the immediate perinatal period required the presence of at least one amino acid substitution mutation, while the presence of two chain terminating mutations invariably resulted in perinatal lethality. The identification of PKHD1 gene provides the basis for direct mutation testing in prenatal diagnosis. However, mutation analysis in ARPKD poses special difficulties due to the huge size of the gene, multiple predicted splice variants and marked allelic heterogeneity.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2007

Author dc:creator

• Pegiazoglou, Ioannis

Contributors dc:contributor

• Zerres, Klaus

• info:eu-repo/classification/ddc/610
• Mutation
• Gen
• Medizin
• ARPKD
• PKHD1

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123954%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:62383