AI Article Synopsis
- - Familial hemiplegic migraine (FHM) is a rare type of migraine linked to specific genes, including CACNA1A, ATP1A2, and SCN1A, but not all cases are tied to these genes.
- - Researchers identified a new variant in the PRRT2 gene (c.938C > T;p.Ala313Val) in a family with hemiplegic migraine symptoms, indicating it may play a significant role in the disease.
- - The PRRT2-A313V variant causes issues with protein stability and localization, suggesting that PRRT2 should be considered in diagnosing hemiplegic migraines, particularly highlighted in a Portuguese patient case.
Article Abstract
Familial hemiplegic migraine (FHM) is a rare autosomal-dominant form of migraine with aura. Three disease-causing genes have been identified for FHM: CACNA1A, ATP1A2 and SCN1A. However, not all families are linked to one of these three genes.PRRT2 variants were also commonly associated with HM symptoms; therefore, PRRT2 is hypothesized as the fourth gene causing FHM. PRRT2 plays an important role in neuronal migration, spinogenesis, and synapse mechanisms during development and calcium-dependent neurotransmitter release. We performed exome sequencing to unravel the genetic cause of migraine in one family, and a novel PRRT2 variant (c.938C > T;p.Ala313Val) was identified with further functional studies to confirm its pathogenicity. PRRT2-A313V reduced protein stability, led to protein premature degradation by the proteasome and altered the subcellular localization of PRRT2 from the plasma membrane (PM) to the cytoplasm. We identified and characterized for the first time in a Portuguese patient, a novel heterozygous missense variant in PRRT2 associated with HM symptoms. We suggest that PRRT2 should be included in the diagnosis of HM.
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