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Analysis of recessive CD2AP and ACTN4 mutations in steroid-resistant nephrotic syndrome

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Abstract

Mutations in podocyte genes have been identified in patients with steroid-resistant nephrotic syndrome (SRNS). Point mutations in the ACTN4 gene cause an autosomal dominant form of human focal segmental glomerular sclerosis (FSGS); however, reports of CD2AP mutations remain scarce. Based on the phenotype of Actn4 and Cd2ap null mice, we aimed to define the role of recessive CD2AP and ACTN4 mutations in a cohort of children with SRNS for which NPHS1, NPHS2, and PLCE1 mutations had been previously excluded. CD2AP and ACTN4 mutational analysis was performed in 42 children from 35 unrelated families. The median age of disease onset was 20 (range 0–102) months. Sixteen patients reached end-stage kidney disease at a median age of 84 (range 4–161) months. Renal histology showed FSGS lesions and minimal glomerular changes in 49% and 20% of patients, respectively. Microsatellite marker analysis excluded linkage to the CD2AP locus in 26 families and to the ACTN4 locus in 31 families. No disease-causing mutations were identified in the remaining families. Recessive CD2AP and ACTN4 mutations are rare in children with SRNS. The absence of mutations in this study suggests that there are other genetic causes of SRNS that still need to be identified.

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Acknowledgements

This research was supported by the Programme Hospitalier de Recherche Clinique AOM02123 and the Association pour l’utilisation du Rein Artificiel (AURA). This study was made possible through a Fonds de la Recherche en Santé Québec (FRSQ) grant accorded to GB and an International Society of Nephrology Fellowship awarded to EM.

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Authors and Affiliations

  1. Inserm, U574, Hôpital Necker-Enfants Malades, Paris, France

    Geneviève Benoit, Eduardo Machuca, Fabien Nevo, Olivier Gribouval, David Lepage & Corinne Antignac

  2. CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada

    Geneviève Benoit

  3. Pontificia Universidad Católica de Chile, Escuela de Medicina, Santiago, Chile

    Eduardo Machuca

  4. Université Paris Descartes, Faculté de Médecine Paris Descartes, Paris, France

    Corinne Antignac

  5. Assistance Publique-Hôpitaux de Paris (AP-HP), Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France

    Corinne Antignac

  6. Inserm U574, 6e étage, Tour Lavoisier, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015, Paris, France

    Corinne Antignac

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  1. Geneviève Benoit
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  2. Eduardo Machuca
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  6. Corinne Antignac
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Correspondence to Corinne Antignac.

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Benoit, G., Machuca, E., Nevo, F. et al. Analysis of recessive CD2AP and ACTN4 mutations in steroid-resistant nephrotic syndrome. Pediatr Nephrol 25, 445–451 (2010). https://doi.org/10.1007/s00467-009-1372-x

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  • DOI: https://doi.org/10.1007/s00467-009-1372-x

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