title: Focal segmental glomerulosclerosis in a patient homozygous for a CD2AP mutation.
abstract: Focal segmental glomerulosclerosis (FSGS) is a histologic diagnosis in several kidney diseases characterized by proteinuria and a severe decrease in kidney function. Mutations in several genes were found in patients with primary FSGS, one of which is a CD2-associated protein CD2AP (originally referred to as CMS). This gene encodes an adaptor protein that plays a role in endocytosis, cell motility, and cell survival. Mice deficient in Cd2ap (the mouse homolog) die due to kidney failure, while heterozygous mice develop lesions similar to those of FSGS patients. In the kidney, CD2AP regulates the actin cytoskeleton. The only previously described patient with CD2AP mutation had a severely truncated protein. In this study, we describe a patient with a novel mutation resulting in a premature stop codon yielding a protein truncated by only 4%. This shortened CD2AP protein displays a significantly decreased F-actin binding efficiency in vitro with no expression of the mutated allele in the patient's lymphocytes. Heterozygous expression of the CD2AP mutation in both parents did not lead to any kidney pathology, as both have normal glomerular filtration rates and no proteinuria.
authors: Department of Pediatric Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: M M
authors: MM
authors: Löwik
authors: P J T A
authors: PJ
authors: Groenen
authors: I
authors: I
authors: Pronk
authors: M R
authors: MR
authors: Lilien
authors: R
authors: R
authors: Goldschmeding
authors: H B
authors: HB
authors: Dijkman
authors: E N
authors: EN
authors: Levtchenko
authors: L A
authors: LA
authors: Monnens
authors: L P
authors: LP
authors: van den Heuvel
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000595:Amino Acid Sequence; D001665:Binding Sites; D001706:Biopsy; D002102:Cadaver; D002675:Child, Preschool; D018388:Codon, Terminator / Q000235:genetics; D003241:Consanguinity; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D006720:Homozygote; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D016030:Kidney Transplantation; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D021141:Nucleic Acid Amplification Techniques; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D016896:Treatment Outcome
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D018388:Codon, Terminator; D003598:Cytoskeletal Proteins