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.

CASE PRESENTATION:

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.

CONCLUSION:

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: Antonio Orlacchio, Paolo Calabresi, Adriana Rum, Anna Tarzia, Anna Maria Salvati, Toshitaka Kawarai, Alessandro Stefani, Antonio Pisani, Giorgio Bernardi, Paolo Cianciulli, Patrizia Caprari
• Journal: BMC neurology (BMC Neurol) Vol. 7 Pg. 4 (Feb 13 2007) ISSN: 1471-2377 [Electronic] England
• PMID: 17298666 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytoskeletal Proteins
• Membrane Proteins
• erythrocyte membrane band 4.1 protein

Topics

• Adult
• Aged
• Chorea (diagnosis, genetics)
• Cytoskeletal Proteins (genetics)
• DNA Mutational Analysis
• Female
• Genetic Predisposition to Disease (genetics)
• Heterozygote
• Humans
• Male
• Membrane Proteins (genetics)
• Mutation
• Pedigree
• Polymorphism, Single Nucleotide (genetics)