Abstract
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.
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Authors and Affiliations
Contributions
Giacomo Baso and Francesco Mele acquired clinical data, analyzed and interpreted all data, and drafted the manuscript. Leonardo Pantoni analyzed and interpreted all data and reviewed the manuscript. Elda Del Giudice and Alberta Leon conducted the genetic analysis, analyzed and interpreted genetic data, and reviewed the manuscript.
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Informed consent was given by the patient described in the case report. All data presented in the manuscript have been collected in routine clinical practice.
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The authors declare no competing interests.
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Baso, G., Mele, F., Del Giudice, E. et al. A novel CACNA1A R2201W variant in a woman with hemiplegic migraine. Neurol Sci 44, 3299–3302 (2023). https://doi.org/10.1007/s10072-023-06839-0
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DOI: https://doi.org/10.1007/s10072-023-06839-0