Neuroacanthocytosis associated with a defect of the 4.1R membrane protein

doi:10.1186/1471-2377-7-4

BMC Neurology

Volume 7

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Orlacchio A
Calabresi P
Rum A
Tarzia A
Salvati AM
Kawarai T
Stefani A
Pisani A
Bernardi G
Cianciulli P
Caprari P

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Orlacchio A
Calabresi P
Rum A
Tarzia A
Salvati AM
Kawarai T
Stefani A
Pisani A
Bernardi G
Cianciulli P
Caprari P
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Case report

Neuroacanthocytosis associated with a defect of the 4.1R membrane protein

Antonio Orlacchio¹^,2 , Paolo Calabresi³^,4 , Adriana Rum² , Anna Tarzia⁵ , Anna Maria Salvati⁵ , Toshitaka Kawarai⁶ , Alessandro Stefani² , Antonio Pisani²^,4 , Giorgio Bernardi¹^,2^,4 , Paolo Cianciulli⁷ and Patrizia Caprari⁵

¹Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello (CERC) – Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy

²Dipartimento di Neuroscienze, Neurologia, Università di Roma "Tor Vergata", Rome, Italy

³Dipartimento di Specialità Medico-Chirurgiche e Sanità Pubblica, Neurologia, Università di Perugia, Perugia, Italy

⁴Laboratorio di Neurofisiologia Sperimentale, Centro Europeo di Ricerca sul Cervello (CERC) – Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy

⁵Dipartimento di Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, Rome, Italy

⁶Department of Neurology, Hyogo Brain and Heart Center, Himeji city, Hyogo prefecture, Japan

⁷Day Hospital Talassemici, Ospedale S. Eugenio, Rome, Italy

author email corresponding author email

BMC Neurology 2007, 7:4doi:10.1186/1471-2377-7-4


Published:	13 February 2007

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.