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01-02-2014 | Original Article

Cost-effective PKHD1 genetic testing for autosomal recessive polycystic kidney disease

Authors: Paola Krall, Cristina Pineda, Patricia Ruiz, Laia Ejarque, Teresa Vendrell, Juan Antonio Camacho, Santiago Mendizábal, Artur Oliver, José Ballarín, Roser Torra, Elisabet Ars

Published in: Pediatric Nephrology | Issue 2/2014

Abstract

Background

Genetic diagnosis of autosomal recessive polycystic kidney disease (ARPKD) is challenging due to the length and allelic heterogeneity of the PKHD1 gene. Mutations appear to be clustered at specific exons, depending on the geographic origin of the patient. We aimed to identify the PKHD1 exons most likely mutated in Spanish ARPKD patients.

Methods

Mutation analysis was performed in 50 ARPKD probands and nine ARPKD-suspicious patients by sequencing PKHD1 exons arranged by their reported mutation frequency. Haplotypes containing the most frequent mutations were analyzed. Other PKD genes (HNF1B, PKD1, PKD2) were sequenced in PKHD1-negative cases.

Results

Thirty-six different mutations (concentrated in 24 PKHD1 exons) were detected, giving a mutation detection rate of 86 %. The screening of five exons (58, 32, 34, 36, 37) yielded a 54 % chance of detecting one mutation; the screening of nine additional exons (3, 9, 39, 61, 5, 22, 26, 41, 57) increased the chance to 76 %. The c.9689delA mutation was present in 17 (34 %) patients, all of whom shared the same haplotype. Two HNF1B mutations and one PKD1 variant were detected in negative cases.

Conclusions

Establishing a PKHD1 exon mutation profile in a specific population and starting the analysis with the most likely mutated exons might significantly enhance the efficacy of genetic testing in ARPKD. Analysis of other PKD genes might be considered, especially in suspicious cases.

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Title: Cost-effective PKHD1 genetic testing for autosomal recessive polycystic kidney disease
Authors: Paola Krall
Cristina Pineda
Patricia Ruiz
Laia Ejarque
Teresa Vendrell
Juan Antonio Camacho
Santiago Mendizábal
Artur Oliver
José Ballarín
Roser Torra
Elisabet Ars
Publication date: 01-02-2014
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 2/2014
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-013-2657-7

At a glance: The STEP trials

Springer Medicine

Cost-effective PKHD1 genetic testing for autosomal recessive polycystic kidney disease

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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