A novel CACNA1A R2201W variant in a woman with hemiplegic migraine.
CACNA1A
Cerebral small vessel disease
Familial hemiplegic migraine
Genetic migraine
Journal
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
ISSN: 1590-3478
Titre abrégé: Neurol Sci
Pays: Italy
ID NLM: 100959175
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
02
02
2023
accepted:
30
04
2023
medline:
11
8
2023
pubmed:
6
5
2023
entrez:
6
5
2023
Statut:
ppublish
Résumé
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. 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. 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.
Identifiants
pubmed: 37148334
doi: 10.1007/s10072-023-06839-0
pii: 10.1007/s10072-023-06839-0
doi:
Substances chimiques
CACNA1A protein, human
0
Calcium Channels
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3299-3302Informations de copyright
© 2023. Fondazione Società Italiana di Neurologia.
Références
Olesen J, Bes A, Kunkel R et al (2013) The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 33:629–808. https://doi.org/10.1177/0333102413485658
doi: 10.1177/0333102413485658
Ducros A, Denier C, Joutel A et al (2001) The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel. N Engl J Med 345:17–24. https://doi.org/10.1056/nejm200107053450103
doi: 10.1056/nejm200107053450103
pubmed: 11439943
Indelicato E, Boesch S (2021) From genotype to phenotype: expanding the clinical spectrum of CACNA1A variants in the era of next generation sequencing. Front Neurol 12:639994. https://doi.org/10.3389/fneur.2021.639994
Hommersom MP, van Prooije TH, Pennings M et al (2022) The complexities of CACNA1A in clinical neurogenetics. J Neurol 269:3094–3108. https://doi.org/10.1007/s00415-021-10897-9
doi: 10.1007/s00415-021-10897-9
pubmed: 34806130
Klockgether T (2008) The clinical diagnosis of autosomal dominant spinocerebellar ataxias. Cerebellum 7:101–105. https://doi.org/10.1007/s12311-008-0023-2
doi: 10.1007/s12311-008-0023-2
pubmed: 18418679
Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424. https://doi.org/10.1038/gim.2015.30
doi: 10.1038/gim.2015.30
pubmed: 25741868
pmcid: 4544753
National Health Institute - ClinVar (2022) NM_001127222.2(CACNA1A):c.6601C>T (p.Arg2201Trp). https://www.ncbi.nlm.nih.gov/clinvar/RCV000443580/ . Accessed 22 Oct 2022
Jen JC (2021) Familial Hemiplegic Migraine. In: GeneReviews®. https://www.ncbi.nlm.nih.gov/books/NBK1388/ . Accessed 1 Nov 2022
Dziewulska D, Kierdaszuk B (2018) Ultrastructural changes in microvessels in familial hemiplegic migraine with CACNA1A mutation. Clin Neuropathol 37:283–287. https://doi.org/10.5414/NP300619
doi: 10.5414/NP300619
pubmed: 30148448