RESUMEN
Repeated evaluation of biotinidase (BTD) activity was carried out for a long-term follow-up in patients with hepatic glycogen storage diseases (GSDs). The results indicated inter-intra variability among the GSD-Ia, GSD-III and GSD-IX patients. In addition, a c.1330G>C transversion in the BTD gene, resulting in a p.Asp444His substitution was detected in one allele of a GSD-Ia patient with sustained normal enzyme activity. Thus far, it is necessary to be cautious in the interpretation of the results of BTD activity as a presumptive GSD diagnostic element. It is not known why plasma BTD activity increases in GSDs patients, or the clinical importance of the increment. When viewed from a global perspective, there are some lines of biotin biology that could indicate a relationship between BTD´s behavior and GSDs.
Asunto(s)
Biotinidasa/sangre , Enfermedad del Almacenamiento de Glucógeno/enzimología , Hígado/enzimología , Argentina , Biomarcadores/sangre , Biotinidasa/genética , Estudios de Casos y Controles , Análisis Mutacional de ADN , Genotipo , Enfermedad del Almacenamiento de Glucógeno/sangre , Enfermedad del Almacenamiento de Glucógeno/diagnóstico , Enfermedad del Almacenamiento de Glucógeno/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/enzimología , Enfermedad del Almacenamiento de Glucógeno Tipo III/enzimología , Humanos , Mutación , Fenotipo , Regulación hacia ArribaRESUMEN
A new splicing site substitution (c.985-1G>C) in the glucose-6-phosphate translocase (G6PT1) gene was detected in both alleles of an Argentinean patient. This mutation was associated with an unusual GSD-Ib phenotype without neutropenia. A PCR-based cDNA analysis showed that the c.985-1G>C mutation produced two abnormal spliced G6PT1 transcripts both encoding hypothetical truncated proteins.
Asunto(s)
Glucosa-6-Fosfato/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Proteínas de Transporte de Membrana/genética , Adolescente , Adulto , Empalme Alternativo , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Preescolar , Femenino , Humanos , Datos de Secuencia Molecular , Neutropenia/genética , Mutación Puntual , Sitios de Empalme de ARN/genéticaRESUMEN
Glycogen storage disease type Ia (GSD-Ia) is caused by deleterious mutations in the glucose-6-phosphatase gene (G6PC). A molecular study of this gene was carried out in 11 Argentinean patients from 8 unrelated families. Four missense (p.Gln54Pro, p.Arg83Cys, p.Thr16Arg, and p.Tyr209Cys) and one deletion (c.79delC) mutations have been identified. Two novel mutations, p.Thr16Arg (c.47C>G) located within the amino-terminal domain and p.Tyr209Cys (c.626A>G) situated in the sixth transmembrane helix, were uncovered in this study. Site-directed mutagenesis and transient expression assays demonstrated that both p.Thr16Arg and p.Tyr209Cys mutations abolished enzymatic activity as well as reduced G6Pase stability.
