Severe MDC1A congenital muscular dystrophy due to a splicing mutation in the LAMA2 gene resulting in exon skipping and significant decrease of mRNA level.
Genet Test
; 11(3): 199-207, 2007.
Article
en En
| MEDLINE
| ID: mdl-17949279
ABSTRACT
Congenital muscular dystrophies (CMDs) are a clinically and genetically heterogeneous group of neuromuscular disorders, with autosomal recessive inheritance. We report a patient with severe congenital muscular dystrophy and total deficiency in the laminin alpha2 chain. Genetic analyses showed a linkage to the MDC1A locus for the patient's family, and DNA sequencing revealed in the propositus of a new homozygous mutation in the donor splice site of intron 58 of the LAMA2 gene. RT-PCR experiments performed on total RNA from a patient's muscle biopsy showed a complete skipping of exon 58 in LAMA2 cDNA and a significant decrease in the LAMA2 mRNA level. This exon skipping altered the open reading frame of the mutant transcript and generated a premature termination codon (PTC) within exon 59, which potentially elicits the nonsense mRNA to degradation by NMD (nonsense-mediated mRNA decay). However, the residual exon 58-lacking mRNA could potentially be translated, and the resulting truncated alpha2 chain would lack its LG4 and LG5 domains that are involved in binding with alpha-dystroglycan. These results demonstrate the utility of mRNA analysis to understand the mutation primary impact and the disease phenotype in the patients.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
ARN Mensajero
/
Empalme del ARN
/
Exones
/
Laminina
/
Distrofias Musculares
/
Mutación
Límite:
Child, preschool
/
Humans
/
Male
Idioma:
En
Revista:
Genet Test
Asunto de la revista:
GENETICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Túnez