Characterization and mRNA expression analysis of a novel ARG1 splicing mutation causing hyperargininemia.
Clin Biochem
; 48(18): 1273-6, 2015 Dec.
Article
en En
| MEDLINE
| ID: mdl-26169240
ABSTRACT
OBJECTIVES:
Biallelic mutations in the ARG1 gene result in an uncommon autosomal recessive inborn defect of the urea cycle known as hyperargininemia (OMIM #207800). ARG1 splicing mutations are not reported often, and they are probably related to a more severe phenotype than missense mutations. In this article, we describe the results of molecular studies in a young hyperargininemia patient carrying a novel splicing mutation in ARG1. DESIGN ANDMETHODS:
Molecular analyses included PCR amplification and direct nucleotide sequencing of the ARG1 gene. RT-PCR analysis was performed to investigate the effect of the mutation in mRNA splicing and in the expression of ARG1 isoforms.RESULTS:
Mutational analysis identified a novel homozygous ARG1 IVS4-1G>C point mutation in the patient's DNA. Blood leukocyte mRNA was analyzed to demonstrate the splicing defect caused by this mutation. Sequencing of ARG1 RT-PCR products allowed the characterization of a mutated transcript retaining 51-bp from intron 4. In addition, two new, alternatively spliced ARG1 transcripts lacking either exon 4 or exons 4 and 5 were identified in mRNA from the patient and from controls.CONCLUSIONS:
Our results expand the mutational spectrum in hyperargininemia patients and indicate that the novel splicing mutation results in an aberrant transcript retaining intronic sequences. Two novel alternatively spliced ARG1 transcripts were also recognized.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arginasa
/
ARN Mensajero
/
Mutación Puntual
/
Hiperargininemia
Tipo de estudio:
Prognostic_studies
Límite:
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Clin Biochem
Año:
2015
Tipo del documento:
Article
País de afiliación:
México