Pubblicazioni

Autori:

Yousaf, Muhammad Abrar; Scartezzini, Arianna; Colombo, Chiara; Bachetti, Tiziana; Sarto, Elisa; Bella, Daniela Di; Lorenzi, Pamela; Tinazzi, Michele; Fabrizi, Gian Maria; Vattemi, Gaetano; Savoia, Anna

Titolo:

A novel de novo GFAP variant causes a juvenile-onset Alexander disease with bilateral vocal cord paralysis

Anno:

2025

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

Elettronico

Referee:

Sì

Nome rivista:

Gene

ISSN Rivista:

0378-1119

N° Volume:

951

Editore:

Elsevier

Intervallo pagine:

1-16

Parole chiave:

Alexander disease; Juvenile onset; Leukodystrophy; Mutation; glial fibrillary acidic protein (GFAP)

Breve descrizione dei contenuti:

Alexander disease (AxD), an autosomal dominant leukodystrophy, is caused by mutations in the GFAP, the gene encoding glial fibrillary acidic protein (GFAP). The disease, classified by age of onset into infantile, juvenile, and adult forms, is characterized by white matter degeneration and astrocytic inclusions called Rosenthal fibers. A patient underwent clinical, radiological, and molecular analyses to confirm a suspected diagnosis of AxD. The functional effect of the variant identified was tested using computational tools and in HeLa and astrocytoma cell lines. We report a case of juvenile AxD that clinically developed acute respiratory distress due to bilateral vocal cord paralysis. Brain and spinal cord MRI revealed the typical findings of the disease, including bulbospinal atrophy and T2-weighted hyperintensities in the frontal periventricular white matter. Molecular genetic testing identified a novel de novo c.713 T > G (p.I238S) variant of GFAP. In silico analyses revealed that the variant at evolutionarily conserved residue likely affects protein function. In vitro assays confirmed its pathogenic effect, showing that p.I238S protein expression significantly associates with aggregate formation in cellular models. Extending the clinical and molecular characterization of new cases of AxD is an important achievement to better characterize the disease.

Note:

First published online: 03 March 2025

Pagina Web:

https://doi.org/10.1016/j.gene.2025.149388

Id prodotto:

144559

Handle IRIS:

11562/1156670

ultima modifica:

5 aprile 2025

Citazione bibliografica:

Yousaf, Muhammad Abrar; Scartezzini, Arianna; Colombo, Chiara; Bachetti, Tiziana; Sarto, Elisa; Bella, Daniela Di; Lorenzi, Pamela; Tinazzi, Michele; Fabrizi, Gian Maria; Vattemi, Gaetano; Savoia, Anna, A novel de novo GFAP variant causes a juvenile-onset Alexander disease with bilateral vocal cord paralysis «Gene» , vol. 951 , 2025 , pp. 1-16

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo