Exome Sequencing of a Portuguese Cohort of Frontotemporal Dementia Patients: Looking Into the ALS-FTD Continuum.

INTRODUCTION

Frontotemporal dementia (FTD) is considered to be part of a continuum with amyotrophic lateral sclerosis (ALS). Many genes are associated with both ALS and FTD. Yet, many genes associated with ALS have not been shown to cause FTD. We aimed to study a Portuguese cohort of FTD patients, searching for variants in genes associated with both FTD and/or ALS.

METHODS

We included 57 thoroughly characterized index FTD patients from our memory clinic, who were not carriers of pathogenic variants in or . We performed exome sequencing and 1) prioritized potential FTD and ALS causing variants by using Exomiser to annotate and filter results; and 2) looked specifically at rare variability in genes associated with FTD (excluding and ) and/or ALS.

RESULTS

We identified 13 rare missense variants in 10 patients (three patients had two variants) in the following genes: and . We found an additional frameshift variant on in one patient. variant ( p.Arg1112His) gathered enough evidence to be classified as likely pathogenic by the ACMG criteria.

DISCUSSION

We report, for the first time, an expanded study of genes known to cause FTD-ALS, in the Portuguese population. Potentially pathogenic variants in and were identified in FTD patients. These findings provide additional evidence for the potential role of rare variability in ALS-associated genes in FTD, expanding the genetic spectrum between the two diseases.