AI Article Synopsis
- - This study investigates genotype-phenotype interactions in Familiar Hemiplegic Migraine type 2 (FHM2) and presents a new missense variant (L425H) in the ATP1A2 gene within an Italian family, characterized by mild symptoms.
- - The identified variant is highly penetrant, with all affected family members showing the aura phenotype, and in silico analysis suggests it may alter the protein's 3D structure.
- - The authors highlight that milder FHM phenotypes are underrepresented in literature and can be misdiagnosed as sporadic migraines, pointing to the need for further research into genetic and functional aspects of these variants.
Article Abstract
Background: The mechanisms of genotype-phenotype interaction in Familiar Hemiplegic migraine type 2 (FHM2) are still far from clear. Different ATP1A2 mutations have been described, with a spectrum of phenotypes ranging from mild to severe. No genotype-phenotype correlations have been attempted.
Case Presentation: We describe an Italian family with FHM and a missense ATP1A2 variant (L425H) not previously described. The clinical picture was mild in all the affected members.
Conclusions: Co-segregation of the variant with the aura phenotype was complete in this family, suggesting a 100% penetrance. In silico protein prediction softwares indicate that this variant may change the 3D structure of ATPA1A2 at the cytoplasmic loop between the two central transmembrane helices. Milder FHM phenotypes are rarely reported in literature, likely because case reports are biased towards the most severe phenotypes, with milder forms possibly misdiagnosed as sporadic migraine with aura forms (MAs), even with complex auras. Further studies taking into account intra-familiar variability and functional consequences on the channel protein may help clarify genotype-phenotype correlations.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953819 | PMC |
| http://dx.doi.org/10.1186/s10194-021-01221-x | DOI Listing |
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