The heterozygous deletion c.1509_1510delAG in exon 14 of FUS causes an aggressive childhood-onset ALS with cognitive impairment.
Neurobiol Aging
; 103: 130.e1-130.e7, 2021 07.
Article
en En
| MEDLINE
| ID: mdl-33637330
ABSTRACT
We report a case of childhood-onset ALS with a FUS gene mutation presenting cognitive impairment and a rapid clinical progression. The patient, an 11-year-old girl, presented with right distal upper limb weakness and mild intellectual disability at the Griffith Mental Development Scales. The disease rapidly worsened and the patient became tetraplegic and bed-ridden 2 years after symptom onset. A c.1509_1510delAG mutation in exon 14 of the FUS gene was detected, resulting in a predicted truncated protein, p.G504Wfs*12, lacking the nuclear localization signal. The levels of FUS mRNA in the proband were not significantly different compared to controls. Western immunoblot analysis showed that one antibody (500-526) detected in the proband ~50% of the amount of FUS protein compared to controls, while 3 other antibodies (2-27, 400-450 and FUS C-terminal), which recognize both wild type and the mutated FUS, detected 60% to 75% of the amount of the protein. These findings indicate that p.G504Wfs*12 FUS is more prone to undergo post-translational modification respect to wild type FUS.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Exones
/
Pérdida de Heterocigocidad
/
Proteína FUS de Unión a ARN
/
Estudios de Asociación Genética
/
Disfunción Cognitiva
/
Heterocigoto
/
Esclerosis Amiotrófica Lateral
/
Mutación
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Child
/
Female
/
Humans
Idioma:
En
Revista:
Neurobiol Aging
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA