Characterization of novel CAPN3 isoforms in white blood cells: an alternative approach for limb-girdle muscular dystrophy 2A diagnosis.
Neurogenetics
; 9(3): 173-82, 2008 Jul.
Article
in En
| MEDLINE
| ID: mdl-18563459
ABSTRACT
Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive disorder caused by mutations in the CAPN3 gene. Its definitive diagnosis is laborious, since the clinical phenotype is often similar to other types of muscular dystrophy and since the CAPN3 gene encompasses a large genomic region with more than 300 pathogenic mutations described to date. In fact, it is estimated that nearly 25% of the cases with a phenotype suggestive of LGMD2A do not have mutations in the CAPN3 gene and that, in up to 22% of the cases, only one mutation is identified. In the present work, we have characterised CAPN3 messenger RNA (mRNA) expression in peripheral blood, and we have performed a retrospective diagnostic study with 26 LGMD2A patients, sequencing a transcript of CAPN3 present in white blood cells (WBCs). The 25% of the mutations presented in this paper (7/28) act modifying pre-mRNA splicing of the CAPN3 transcript, including the first deep-intronic mutation described to date in the CAPN3 gene. Our results determine that the sequencing of CAPN3 transcripts present in WBCs could be applied as a new approach for LGMD2A diagnosis. This method improves and simplifies diagnosis, since it combines the advantages of mRNA analysis in a more accessible and rapidly regenerated tissue. However, the lack of exon 15 in the CAPN3 isoforms present in blood, and the presence of mRNA degradation make it necessary to combine mRNA and DNA analyses in some specific cases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calpain
/
Muscular Dystrophies, Limb-Girdle
/
Leukocytes
/
Muscle Proteins
Type of study:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Neurogenetics
Journal subject:
GENETICA
/
NEUROLOGIA
Year:
2008
Type:
Article
Affiliation country:
Spain