A rare ACAN non-canonical splicing-site intron variant results in familial short stature.
Gene
; 925: 148602, 2024 Oct 20.
Article
en En
| MEDLINE
| ID: mdl-38782218
ABSTRACT
OBJECTIVE:
ACAN gene variants, prevalent monogenic defects linked to short stature, are characterized by impaired cartilage generation in growth plates. We aimed to unravel the genetic basis of short stature in a specific pedigree by investigating the role of a novel non-canonical splicing-site variant, c.630-13G > A, within the ACAN gene.METHOD:
Sanger sequencing was used for pedigree verification, and the effects of this variant on mRNA splicing were analyzed through minigene assay.RESULTS:
The study revealed that this variant led to the creation of a previously unreported splice site in the fourth intron, resulting in the incorporation of an 11 bp sequence from the intron into the final transcript. This alteration led to a frameshift and formation of a premature termination codon, impacting the structure of the aggrecan protein.CONCLUSIONS:
We document the pathogenicity of an ACAN non-canonical splicing-site variant, emphasizing the significance of considering intronic variants during genetic testing.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linaje
/
Intrones
/
Empalme del ARN
/
Agrecanos
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Gene
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Países Bajos