A novel CACNA1A R2201W variant in a woman with hemiplegic migraine

Introduction Familial hemiplegic migraine type 1 (FHM1) is a monogenic rare disease that is characterized by migraine attacks accompanied by unilateral weakness and is caused by mutations in the CACNA1A gene. We report the case of a patient with a clinical history consistent with hemiplegic migraine...

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Bibliographic Details
Published in:Neurological sciences 2023-09, Vol.44 (9), p.3299-3302
Main Authors: Baso, Giacomo, Mele, Francesco, Del Giudice, Elda, Leon, Alberta, Pantoni, Leonardo
Format: Article
Language:English
Subjects:
Brief Communication
CACNA1A protein
Cognitive ability
Comorbidity
Genetic screening
Headache
Heterozygosity
Leukoencephalopathy
Magnetic resonance imaging
Medicine
Medicine & Public Health
Migraine
Missense mutation
Mutation
Neurology
Neuroradiology
Neurosciences
Neurosurgery
Protein structure
Psychiatry
Tryptophan
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Summary:Introduction Familial hemiplegic migraine type 1 (FHM1) is a monogenic rare disease that is characterized by migraine attacks accompanied by unilateral weakness and is caused by mutations in the CACNA1A gene. We report the case of a patient with a clinical history consistent with hemiplegic migraine who underwent genetic testing that revealed a variant in the CACNA1A gene. Case presentation A 68-year-old woman was evaluated for progressive postural instability and subjective cognitive decline. She had suffered from recurrent migraine episodes accompanied by fully reversible unilateral weakness that had started around the age of thirty and had fully disappeared at the time of evaluation. Magnetic resonance imaging (MRI) showed an extensive leukoencephalopathy, with features suggestive of small vessel disease, significantly progressing over the years. Exome sequencing revealed the heterozygous variant c.6601C>T (p.Arg2201Trp) in the CACNA1A gene. This variant, located in a highly conserved region, causes the substitution of arginine with tryptophan at codon 2202 of exon 47, with a high likelihood of a damaging effect on protein activity and/or structure. Discussion This is the first report describing the missense mutation c.6601C>T (p.Arg2201Trp) in heterozygosity in the CACNA1A gene in a patient with clinical features of hemiplegic migraine. The presence of a diffuse leukoencephalopathy on MRI is not typical of hemiplegic migraine and may suggest a phenotypic variant related to this mutation or result from the combined effect of the patient’s comorbidities.
ISSN:1590-1874
1590-3478
DOI:10.1007/s10072-023-06839-0