title: Neuroacanthocytosis associated with a defect of the 4.1R membrane protein.
abstract: BACKGROUND
  Neuroacanthocytosis (NA) denotes a heterogeneous group of diseases that are characterized by nervous system abnormalities in association with acanthocytosis in the patients' blood. The 4.1R protein of the erythrocyte membrane is critical for the membrane-associated cytoskeleton structure and in central neurons it regulates the stabilization of AMPA receptors on the neuronal surface at the postsynaptic density. We report clinical, biochemical, and genetic features in four patients from four unrelated families with NA in order to explain the cause of morphological abnormalities and the relationship with neurodegenerative processes.
  
  
  METHODS
  All patients were characterised by atypical NA with a novel alteration of the erythrocyte membrane: a 4.1R protein deficiency. The 4.1R protein content was significantly lower in patients (3.40 +/- 0.42) than in controls (4.41 +/- 0.40, P < 0.0001), reflecting weakened interactions of the cytoskeleton with the membrane. In patients IV:1 (RM23), IV:3 (RM15), and IV:6 (RM16) the 4.1 deficiency seemed to affect the horizontal interactions of spectrin and an impairment of the dimer self-association into tetramers was detected. In patient IV:1 (RM16) the 4.1 deficiency seemed to affect the skeletal attachment to membrane and the protein band 3 was partially reduced.
  
  
  CONCLUSIONS
  A decreased expression pattern of the 4.1R protein was observed in the erythrocytes from patients with atypical NA, which might reflect the expression pattern in the central nervous system, especially basal ganglia, and might lead to dysfunction of AMPA-mediated glutamate transmission.
authors.affiliation: Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello--Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia, Rome, Italy. a.orlacchio@hsantalucia.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Orlacchio
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.forename: Adriana
authors.initials: A
authors.lastname: Rum
authors.forename: Anna
authors.initials: A
authors.lastname: Tarzia
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Salvati
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Kawarai
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Paolo
authors.initials: P
authors.lastname: Cianciulli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Caprari
mesh_terms: D000328:Adult; D000368:Aged; D002819:Chorea / Q000175:diagnosis / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C028841:erythrocyte membrane band 4.1 protein