Identification of a novel splicing-altering LAMP2 variant in a Chinese family with Danon disease.
ESC Heart Fail
; 10(4): 2479-2486, 2023 08.
Article
en En
| MEDLINE
| ID: mdl-37277924
ABSTRACT
AIMS:
This study aimed to identify a novel splicing-altering LAMP2 variant associated with Danon disease. METHODS ANDRESULTS:
To identify the potential genetic mutation in a Chinese pedigree, whole-exome sequencing was conducted in the proband, and Sanger sequencing was performed on the proband's parents. To verify the impact of the splice-site variant, a minigene splicing assay was applied. The AlphaFold2 analysis was used to analyse the mutant protein structure. A splice-site variant (NM_013995.2c.864+5G>A) located at intron 6 of the LAMP2 gene was identified as a potential pathogenic variant. The minigene splicing revealed that this variant causes exon 6 to be skipped, resulting in a truncated protein. The AlphaFold2 analysis showed that the mutation caused a protein twist direction change, leading to conformational abnormality.CONCLUSIONS:
A novel splice-site variant (NM_013995.2c.864+5G>A) located at intron 6 of the LAMP2 gene was identified. This discovery may enlarge the LAMP2 variant spectrum, promote accurate genetic counselling, and contribute to the diagnosis of Danon disease.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Empalme del ARN
/
Enfermedad por Depósito de Glucógeno de Tipo IIb
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
ESC Heart Fail
Año:
2023
Tipo del documento:
Article
País de afiliación:
China