Background Mutations in the calcium channel voltage dependent P/Q-type alpha-1A subunit (CACNA1A) can cause different neurological disorders which share a wide range of symptoms, including episodic ataxia type 2 (EA2), familial hemiplegic migraine (FHM1) and progressive spinocerebellar ataxia (SCA6). Objective To describe a three generations family in which a spectrum of different phenotypes, ranging from SCA6 (proband), to EA2 (proband's mother) to FHM1 (proband's mother and proband's aunt) was found. All of the family members carried a novel CACNA1A missense mutation. Patients and methods A clinical, molecular, neuroradiological and neurophysiological study was carried out in all subjects. Results A single heterozygous base change in exon 9, c1213G -> A, leading to the amino acid substitution pAla405Thr was found to segregate within the family. Brain MRI showed cerebellar and cerebral atrophy signs in all but one mutation carriers. Neurophysiological findings (electroencephalography and evoked potentials) confirmed possible cerebral cortex and white matter involvement regardless of the clinical symptoms displayed. Conclusions This novel CACNA1A mutation adds to the number of mutations associated with a heterogeneous clinical picture in family members. This mutation might affect the interaction between the intracellular loops and the beta subunit, leading to a relatively rapid cell death. In order to explain the wide phenotypic variability observed in this family, it is hypothesised that additional genetic and environmental (hormonal) factors play a role in the pathophysiology of the disease.

A wide spectrum of clinical, neurophysiological and neuroradiological abnormalities in a family with a novel CACNA1A mutation / R. Romaniello, C. Zucca, A. Tonelli, S. Bonato, C. Baschirotto, N. Zanotta, R. Epifanio, A. Righini, N. Bresolin, M. Bassi, R. Borgatti. - In: JOURNAL OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY. - ISSN 0022-3050. - 81:8(2010 Aug), pp. 840-843.

A wide spectrum of clinical, neurophysiological and neuroradiological abnormalities in a family with a novel CACNA1A mutation

N. Bresolin;
2010

Abstract

Background Mutations in the calcium channel voltage dependent P/Q-type alpha-1A subunit (CACNA1A) can cause different neurological disorders which share a wide range of symptoms, including episodic ataxia type 2 (EA2), familial hemiplegic migraine (FHM1) and progressive spinocerebellar ataxia (SCA6). Objective To describe a three generations family in which a spectrum of different phenotypes, ranging from SCA6 (proband), to EA2 (proband's mother) to FHM1 (proband's mother and proband's aunt) was found. All of the family members carried a novel CACNA1A missense mutation. Patients and methods A clinical, molecular, neuroradiological and neurophysiological study was carried out in all subjects. Results A single heterozygous base change in exon 9, c1213G -> A, leading to the amino acid substitution pAla405Thr was found to segregate within the family. Brain MRI showed cerebellar and cerebral atrophy signs in all but one mutation carriers. Neurophysiological findings (electroencephalography and evoked potentials) confirmed possible cerebral cortex and white matter involvement regardless of the clinical symptoms displayed. Conclusions This novel CACNA1A mutation adds to the number of mutations associated with a heterogeneous clinical picture in family members. This mutation might affect the interaction between the intracellular loops and the beta subunit, leading to a relatively rapid cell death. In order to explain the wide phenotypic variability observed in this family, it is hypothesised that additional genetic and environmental (hormonal) factors play a role in the pathophysiology of the disease.
episodic ataxia type-2; calcium-channel; hemiplegic migraine; missense mutation; spinocerebellar ataxia; progressive ataxia; epilepsy; gene; childhood
Settore MED/26 - Neurologia
ago-2010
Article (author)
File in questo prodotto:
File Dimensione Formato  
J Neurol Neurosurg Psychiatry-2010-Romaniello-840-3.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 296.8 kB
Formato Adobe PDF
296.8 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/290984
Citazioni
  • ???jsp.display-item.citation.pmc??? 22
  • Scopus 46
  • ???jsp.display-item.citation.isi??? 41
social impact