Abstract
Background and aimsHemiplegic migraine (HM) is a rare form of migraine characterized by the presence of a motor and other types of aura. HM can be sporadic or familial. Familial hemiplegic migraine (FHM) is an autosomal dominant disorder, classified into 3 subtypes, based on the gene involved (CACNA1A in FHM1, ATP1A2 in FHM2 and SCN1A in FHM3). The clinical presentation is highly heterogeneous and some attacks may be severe.We report the clinical characteristics and genetic analysis of 12 patients belonging to a family with CACNA1A-p.Thr501Met gene mutation.MethodsWe screened for mutations in CACNA1A gene 15 patients belonging to the same family. The exonic sequences of CACNA1A were analyzed using a Tru-seq® Custom Amplicon (TSCA) (Illumina Inc., San Diego, CA) targeted capture and paired end library kit. Sanger sequencing was used to confirm CACNA1A variants and segregation analysis.ResultsCACNA1A-p.Thr501Met mutation was found in 12 of the 15 patients screened, which was compatible with the diagnosis of FHM1.Attacks of hemiplegic migraine were reported by 10 of the 12 subjects (83.33%). Only one subject developed persistent mild cerebellar symptoms and none of the subjects developed cerebellar atrophy.DiscussionThe variant p.Thr501Met was described previously in association with episodic ataxia and rarely with FHM related to cerebellar symptoms. FHM1 has a broad clinical spectrum and about half of the families have cerebellar involvement. In our study, only one patient developed persistent cerebellar deficits.These data suggest that CACNA1A-p.Thr501Met mutation can occur prevalently as hemiplegic migraine.
Highlights
CACNA1A-p.Thr501Met mutation was found in 12 of the 15 patients screened, which was compatible with the diagnosis of FHM1
Hemiplegic migraine (HM) is a rare form of migraine characterized by the presence of a motor aura and other types of aura
We described a large family with CACNA1A-p.Thr501Met mutation whose prevalent clinical expression was hemiplegic migraine
Summary
Hemiplegic migraine (HM) is a rare form of migraine characterized by the presence of a motor aura and other types of aura. According to the International Classification of Headache Disorders-3 (ICHD-3), the disease is classified into 3 subtypes, based on the gene involved. Mutations in the CACNA1A gene, which encodes the alpha-1A subunit of the P/Q type calcium channel, cause FHM1 [1]. Mutations in the ATP1A2 gene, which encodes a catalytic subunit of a sodium/potassium ATPase, cause FHM2. FHM3 is caused by mutations in the SCN1A gene that encodes the alpha subunit of the neuronal voltage-gated sodium channel [1]. Familial hemiplegic migraine (FHM) is an autosomal dominant disorder, classified into 3 subtypes, based on the gene involved (CACNA1A in FHM1, ATP1A2 in FHM2 and SCN1A in FHM3). We report the clinical characteristics and genetic analysis of 12 patients belonging to a family with CACNA1Ap.Thr501Met gene mutation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
