The c.824C>A and c.616dupA mutations in the SLC17a8 gene are associated with auditory neuropathy and lead to defective expression of VGluT3.
Neuroreport
; 32(11): 949-956, 2021 08 04.
Article
en En
| MEDLINE
| ID: mdl-34145196
ABSTRACT
Auditory neuropathy is sensorineural deafness where sound signals cannot be transmitted synchronously from the cochlea to the auditory center. Abnormal expression of vesicle glutamate transporter 3 (VGluT3) encoded by the SLC17a8 gene is associated with the pathophysiology of auditory neuropathy. Although several suspected pathogenic mutations of the SLC17a8 gene have been identified in humans, few studies have confirmed their pathogenicity. Here, we describe the effects of two known suspected pathogenic mutations (c.824C>A and c.616dupA) in the SLC17a8 gene coding VGluT3 protein and analyzed the potential pathogenicity of these mutations. The p.M206Nfs4 and p.A275D changes are caused by c.824C>A and c.616dupA mutations in the cytoplasmic loop, an important structure of VGluT3. To explore the potential pathogenic effects of c.824C>A and c.616dupA mutations, we performed a series of experiments on mRNA levels and protein expression in cell culture. The c.616dupA mutation in the SLC17a8 gene resulted in a significant decrease in transcriptional activity of mRNA, and the expression of VGluT3 was also reduced. The c.824C>A mutation in the SLC17a8 gene resulted in abnormal VGluT3, although this mutation did not affect the transcriptional activity of mRNA. Our results demonstrate that c.824C>A and c.616dupA mutations in the SLC17a8 gene could lead to pathological protein expression of VGluT3 and supported the potential pathogenicity of these mutations.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biología Computacional
/
Proteínas de Transporte Vesicular de Glutamato
/
Pérdida Auditiva Central
/
Mutación
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Neuroreport
Asunto de la revista:
NEUROLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China