Cost-effective PKHD1 genetic testing for autosomal recessive polycystic kidney disease
Por:
Krall, P, Pineda, C, Ruiz, P, Ejarque, L, Vendrell, T, Camacho, JA, Mendizabal, S, Oliver, A, Ballarin, J, Torra, R, Ars, E
Publicada:
1 feb 2014
Resumen:
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.
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.
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.
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.
Filiaciones:
Krall, P:
Univ Autonoma Barcelona, Inst Invest Carlos 3, IIB Sant Pau, Fundacio Puigvert,Mol Biol Lab,REDinREN, Barcelona 08025, Spain
Univ Autonoma Barcelona, Inst Invest Carlos 3, IIB Sant Pau, Fundacio Puigvert,Dept Nephrol,REDinREN, Barcelona 08025, Spain
Pineda, C:
Univ Autonoma Barcelona, Inst Invest Carlos 3, IIB Sant Pau, Fundacio Puigvert,Mol Biol Lab,REDinREN, Barcelona 08025, Spain
Ruiz, P:
Univ Autonoma Barcelona, Inst Invest Carlos 3, IIB Sant Pau, Fundacio Puigvert,Mol Biol Lab,REDinREN, Barcelona 08025, Spain
Ejarque, L:
Univ Autonoma Barcelona, Inst Invest Carlos 3, IIB Sant Pau, Fundacio Puigvert,Mol Biol Lab,REDinREN, Barcelona 08025, Spain
Vendrell, T:
Hosp Valle De Hebron, Programa Med Mol & Genet, Barcelona, Spain
Camacho, JA:
Hosp St Joan de Deu, Pediat Nephrol Dept, Barcelona, Spain
Mendizabal, S:
Hosp Univ La Fe, Pediat Nephrol Dept, Valencia, Spain
Oliver, A:
Univ Autonoma Barcelona, Inst Invest Carlos 3, IIB Sant Pau, Fundacio Puigvert,Mol Biol Lab,REDinREN, Barcelona 08025, Spain
Ballarin, J:
Univ Autonoma Barcelona, Inst Invest Carlos 3, IIB Sant Pau, Fundacio Puigvert,Dept Nephrol,REDinREN, Barcelona 08025, Spain
Torra, R:
Univ Autonoma Barcelona, Inst Invest Carlos 3, IIB Sant Pau, Fundacio Puigvert,Dept Nephrol,REDinREN, Barcelona 08025, Spain
Ars, E:
Univ Autonoma Barcelona, Inst Invest Carlos 3, IIB Sant Pau, Fundacio Puigvert,Mol Biol Lab,REDinREN, Barcelona 08025, Spain
Univ Autonoma Barcelona, Inst Invest Carlos 3, IIB Sant Pau, Fundacio Puigvert,Dept Nephrol,REDinREN, Barcelona 08025, Spain
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