講演情報
[P12-11]進行性核上性麻痺におけるFLNAバリアントのスクリーニング
○久米 広大1, 和泉 唯信2, 織田 雅也3, 小松 研一4, 高橋 牧郎4, 多田 有似1, 鎌田 正紀5, 川上 秀史1 (1.広島大学原爆放射線医科学研究所分子疫学研究分野, 2.徳島大学脳神経内科, 3.ビハーラ花の里病院脳神経内科, 4.北野病院脳神経内科, 5.香川大学神経難病講座)
Background:
Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by tufted astrocyte and accumulation of 4-repeat tau. Because the clinical symptoms are broad, it is difficult to differentiate PSP from other tauopathies including corticobasal degeneration and Alzheimer’s disease. In addition, the pathophysiology of PSP remains unknown. Recently, it has been reported that the variants in FLNA, encoding filamin-A, are associated with PSP.
Objective:
The aim of this study is to confirm the significance of the variants of FLNA in PSP.Methods:
Exome sequencing was performed for nine patients with PSP and five patients with corticobasal syndrome (CBS).The data analysis was performed according to the GATK best practices. The identified variant was validated by Sanger sequencing.
Results:
One patient with PSP had a variant (NM_001110556:c.7055C＞T,p.S2352F). The variant is reported as a rare variant in the gnomAD (allele frequency: 0.000011) and predicted as pathogenic by several tools (CADD score: 25, PolyPhen-2: possibly damaging, MutationTaster: disease causing). In our variant database, a patient with spinocerebellar ataxia had the same variant. No variants in FLNA were identified in patients with CBS. Discussion:
Our findings showed that the variant in FLNA may contribute to the development of PSP.
Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by tufted astrocyte and accumulation of 4-repeat tau. Because the clinical symptoms are broad, it is difficult to differentiate PSP from other tauopathies including corticobasal degeneration and Alzheimer’s disease. In addition, the pathophysiology of PSP remains unknown. Recently, it has been reported that the variants in FLNA, encoding filamin-A, are associated with PSP.
Objective:
The aim of this study is to confirm the significance of the variants of FLNA in PSP.Methods:
Exome sequencing was performed for nine patients with PSP and five patients with corticobasal syndrome (CBS).The data analysis was performed according to the GATK best practices. The identified variant was validated by Sanger sequencing.
Results:
One patient with PSP had a variant (NM_001110556:c.7055C＞T,p.S2352F). The variant is reported as a rare variant in the gnomAD (allele frequency: 0.000011) and predicted as pathogenic by several tools (CADD score: 25, PolyPhen-2: possibly damaging, MutationTaster: disease causing). In our variant database, a patient with spinocerebellar ataxia had the same variant. No variants in FLNA were identified in patients with CBS. Discussion:
Our findings showed that the variant in FLNA may contribute to the development of PSP.