A CACNA1A Exon 36 Mutation in Episodic Ataxia with Absences Is Not Found in 220 Unselected Cases of Idiopathic Generalised Epilepsy
Abstract number :
1.063
Submission category :
Year :
2001
Submission ID :
3035
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
B.A. Chioza, MSc, Department of Psychological Medicine, Institute of Psychiatry, London, United Kingdom; H.J. Wilkie, BSc, Department of Psychological Medicine, Institute of Psychiatry, London, United Kingdom; D. McCormick, MD, Department of Neurology, Ke
RATIONALE: Voltage-gated calcium channels (VGCCs) are formed by [alpha][sub]1[/sub] subunits modulated by [beta], [gamma], [alpha][sub]2[/sub] and [delta] subunits. Mutations in CACNA1A gene (producing the [alpha][sub]1A[/sub] subunit) cause recessive [italic]tottering/leaner[/italic] mouse models of ataxia/spike wave epilepsy and the CACNB4 gene ([beta]subunit) the [italic]lethargic[/italic] phenotype. Several inherited human neurological conditions are due to CACNA1A mutations including familial hemiplegic migraine, episodic ataxia (EA-2) and spinocerebellar ataxia (SCA6). These syndromes may co-exist. A proband with episodic ataxia, learning difficulty and absences was heterozygous for an exon 36 mutation at nucleotide 5733 (CGA to TGA) resulting in Arg1820stop (Eunson et al., 1999). Two mutations in CACNB4 were reported one in a patient with JME and another in two families, one with epilepsy and the other episodic ataxia (Escayg et al., 2000).
We have reported an association in our cohort of idiopathic generalised epilepsy (IGE) with 2 markers in the region of exon 8 of CACNA1A using both case-control and intrafamilial study designs (Chioza et al., 2001). Since then, association of IGE with 4 further nearby markers has supported this finding.
METHODS: DNA was extracted from white Caucasian patients from Kent and Canterbury Hospital. All had generalised spike/wave on EEG, a clinical history consistent with IGE and were unselected for subtype. The CACNA1A exon 36 Arg1820stop mutation was assayed by RFLP using AvaI.
RESULTS: We screened 220 unselected cases of IGE for the presence of the CACNA1A exon 36 Arg1820stop mutation. This mutation was not detected in any of the cases. We are currently screening for the two CACNB4 mutations to investigate their relevance to the common forms of IGE.
CONCLUSIONS: Our failure to detect the CACNA1A exon 36 Arg1820stop mutation in 220 unselected cases suggests that this mutation is unlikely to be relevant to the majority of cases of IGE. Our positive association results with markers in CACNA1A, however, still strongly support this gene being implicated in IGE which we are continuing to investigate.
Support: King[ssquote]s Joint Research Committee,
Epilepsy Research Foundation