Expanding the clinical and genetic spectrum of SQSTM1-related disorders in family with personality disorder and frontotemporal dementia.
Amyotroph Lateral Scler Frontotemporal Degener
; 22(7-8): 552-560, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34009082
ABSTRACT
Objective:
SQSTM1-variants associated with frontotemporal lobar degeneration have been described recently. In this study, we investigated a heterozygous in-frame duplication c.436_462dup p. (Pro146_Cys154dup) in the SQSTM1 gene in a family with a new phenotype characterized by a personality disorder and behavioral variant frontotemporal dementia (bvFTD). We review the literature on frontotemporal dementia (FTD) associated with SQSTM1.Methods:
The index case and relatives were described, and a genetic study through Whole Exome Sequencing was performed. The literature was reviewed using Medline and Web of Science. Case reports, case series, and cohort studies were included if they provided information on SQSTM1 mutations associated with FTD.Results:
Our patient is a 70-year-old man with a personality disorder since youth, familial history of dementia, and personality disorders with a 10-year history of cognitive decline and behavioral disturbances. A diagnosis of probable bvFTD was established, and the in-frame duplication c.436_462dup in the SQSTM1 gene was identified. Segregation analysis in the family confirmed that both affected sons with personality disorder were heterozygous carriers, but not his healthy 65-year-old brother. A total of 14 publications about 57 patients with SQSTM1-related FTD were reviewed, in which the bvFTD subtype was the main phenotype described (66.6%), with a predominance in men (63%) and positive family history in 61.4% of the cases.Conclusions:
We describe a heterozygous in-frame duplication c.436_462dup p.(Pro146_Cys154dup) in the SQSTM1 gene, which affects the zinc-finger domain of p62, in a family with a personality disorder and bvFTD, expanding the genetics and clinical phenotype related to SQSTM1.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Degeneração Lobar Frontotemporal
/
Demência Frontotemporal
/
Esclerose Lateral Amiotrófica
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Aged
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article