Rare variants in TP73 in a frontotemporal dementia cohort link this gene with primary progressive aphasia phenotypes. (21st January 2022)

• Record Type: Journal Article
• Authors: Tábuas‐Pereira, Miguel; Santana, Isabel; Almeida, Maria Rosário; Durães, João; Lima, Marisa; Duro, Diana; Kun‐Rodrigues, Célia; Bras, Jose; Guerreiro, Rita
• Is Part Of: European journal of neurology. Volume 29:Number 5(2022)
• Page Start: 1524
• Page End: 1528
• Publication Date: 2022-01-21
• Subjects: amyotrophic lateral sclerosis -- aphasia -- frontotemporal dementia -- gene -- TP73; Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.15248
• Languages: English
• ISSNs: 1351-5101

Abstract

Abstract: Background and purpose: TP73 was recently reported to cause amyotrophic lateral sclerosis (ALS). ALS and frontotemporal dementia (FTD) are considered to form part of a continuum. We aimed to investigate whether TP73 variants may be associated with FTD. Methods: We studied a thoroughly investigated cohort of 65 Portuguese patients with frontotemporal dementia using whole‐exome sequencing. The patients had no other known genetic cause for their disease (C9orf72 expansion was also excluded). Results: Of the 65 patients studied, two had rare variants in TP73 (p.Gly605Ser and p.Arg347Trp). Both variants had minor allele frequency <0.001 and were predicted to be pathogenic in silico . The two patients displayed a phenotype that included predominant language impairment, suggestive of non‐fluent progressive aphasia. Conclusion: We show that two thoroughly studied patients without other known genetic changes harbored TP73 rare variants, which are pathogenic in silico . This adds evidence to support the role of TP73 in the ALS–FTD spectrum, especially in primary progressive aphasia cases. Abstract : Of 65 patients with frontotemporal dementia studied by whole‐exome sequencing, we found two patients harboring rare variants in TP73 (p.Gly605Ser and p.Arg347Trp). These TP73 rare variant carriers showed a phenotype that included predominant language impairment, suggestive of non‐fluent progressive aphasia. This adds evidence to support the role of TP73 in the ALS–FTD spectrum, especially in primary progressive aphasia cases.