Genetic screening of ANXA11 in Korean patients with Frontotemporal dementia syndrome

Abstract

AbstractBackgroundPathogenic variants of ANXA11 have recently been identified in patients with ALS and ALS‐FTD in ALS cohorts. However, it is uncertain how prevalent the pathogenic variant of ANXA11 is in FTD syndrome. Thus, we performed genetic screening of ANXA11 in Korean patients with FTD to investigate the frequencies and clinical manifestations of ANXA11 mutations in Asian FTD population.MethodWe searched pathogenic variants of ANXA11 in whole exome database of Korean patients with FTD syndrome. Out of a total of 240 patients, 179 patients had been included in the previous Korean FTD genetic screening studies and the rest 61 patients have currently been enrolled in an ongoing longitudinal study of early onset dementia and family members‐FTD (LEAF‐FTD).ResultOne pathogenic variant in ANXA11, c.119A>G (p.D40G), was identified in three patients with right‐predominant svPPA. One of them has recently been reported elsewhere. They were all women and mean age of onset was 63 years old. Two of them had family history of dementia in first‐degree relatives. One patient showed dysarthria and motor weakness 3 years after the onset of symptoms who might have been presumed to have svPPA‐ALS, while the other two had no neurological deficits. Initial neuropsychological test results revealed selective impairments of naming and verbal memory. Brain MRIs demonstrated cortical atrophy in bilateral anterior temporal areas, worse on the right. One patient carried a pathogenic variant, p.V180I of PRNP as well as p.D40G of ANXA11, however, did not show any clinical features of CJD. Other than p.D40G variant, we found two variants of unknown significance of ANXA 11 in one patient with nfvPPA (c.1336‐6C>G) and the other with bvFTD (c.654G>A, p.T218 = ).ConclusionANXA11 mutations account for 0.8% of familial and 1.7% of sporadic ALS in European populations. The p.D40G variant identified in this study (1.25%, 3/240) had already been reported in both familial and sporadic ALS. Although the phenotypic variation of ANXA11 in FTD or FTD‐ALS syndrome remains unclear, our results suggest that right‐predominant svPPA may be a common FTD or FTD‐ALS manifestation in p.D40G variant. Further genetic screening of ANXA11 in Caucasian FTD cohort is needed.