Portal de investigación
Cost-effective PKHD1 genetic testing for autosomal recessive polycystic kidney disease
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Krall, P
- Pineda, C
- Ruiz, P
- Ejarque, L
- Vendrell, T
- Camacho, JA
- Oliver, A
- Ballarin, J
- Torra, R
- Ars, E
Abstract
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.
Datos de la publicación
- ISSN/ISSNe:
- 0931-041X, 1432-198X
- Tipo:
- Article
- Páginas:
- 223-234
- PubMed:
- 24162162
- Factor de Impacto:
- 1,174 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
PEDIATRIC NEPHROLOGY SPRINGER
Citas Recibidas en Web of Science: 14
Documentos
- No hay documentos
Filiaciones
Keywords
- ARPKD; PKHD1; Genetic testing; Exon mutation profile
Proyectos y Estudios Clínicos
ESTUDIO ALEATORIZADO, DOBLE CIEGO, CONTROLADO CON PLACEBO PARA EVALUAR LA EFICACIA Y SEGURIDAD DE CINACALCET HCL EN PACIENTES PEDIÁTRICOS CON ENFERMEDAD RENAL CRÓNICA E HIPERPARATIROIDISMO SECUNDARIO EN DIÁLISIS
Investigador Principal: JESÚS LUCAS GARCÍA
20070208 . 2012
ESTUDIO EN FASE 3 PROSPECTIVO, MULTICENTRICO, ALEATORIZADO, DOBLE CIEGO Y CONTROLADO CON PLACEBO PARA EVALUAR LA FARMACOCINETICA, LA SEGURIDAD Y LA EFICACIA DE PARICALCITOL EN CAPSULAS EN CUANTO A LA REDUCCION DE LA CONCENTRACION SERICA DE HORMONA PARATIR OIDEA INTACTA EN NIÑOS Y ADOLESCENTES DE ENTRE 10 Y 16 AÑOS CON NEFROPATIA CRONICA MODERADA O GRAVE
Investigador Principal: SANTIAGO MENDIZABAL OTEIZA
M10-149 . 2011
UN ESTUDIO OBSERVACIONAL, NO INTERVENCIONISTA, MULTICÉNTRICO Y MULTINACIONAL DE PACIENTES CON SÍNDROME HEMOLÍTICO URÉMICO ATÍPICO (REGISTRO DE SHUA).
Investigador Principal: ELENA ROMÁN ORTIZ
ALE-ECU-2012-01 . 2013
Cita
Krall P,Pineda C,Ruiz P,Ejarque L,Vendrell T,Camacho JA,MENDIZABAL S,Oliver A,Ballarin J,Torra R,Ars E. Cost-effective PKHD1 genetic testing for autosomal recessive polycystic kidney disease. Pediatr Nephrol. 2014. 29. (2):p. 223-234. IF:2,856. (1).