title: Analysis of recessive CD2AP and ACTN4 mutations in steroid-resistant nephrotic syndrome.
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.
authors: Inserm, U574, Hôpital Necker-Enfants Malades, Paris, France.
authors: Geneviève
authors: G
authors: Benoit
authors: Eduardo
authors: E
authors: Machuca
authors: Fabien
authors: F
authors: Nevo
authors: Olivier
authors: O
authors: Gribouval
authors: David
authors: D
authors: Lepage
authors: Corinne
authors: C
authors: Antignac
mesh_terms: D000185:Actinin / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D017668:Age of Onset; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004351:Drug Resistance; D005006:Ethnicity; D005260:Female; D006801:Humans; D007223:Infant; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000627:therapeutic use*
chemical_list: C111453:ACTN4 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000893:Anti-Inflammatory Agents; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D013256:Steroids; D000185:Actinin; D004247:DNA