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Análisis mutacional de la acondroplasia en 20 pacientes colombianos
Mutational analysis of achondroplasia in 20 Colombian patients
Palabras clave:
análisis mutacional de ADN, acondroplasia, anomalías autosómicas, mutación, fenotipo. (es)DNA mutational analysis, achondroplasia, chromosome aberrations, mutation, phenotype. (en)
Antecedentes. La acondroplasia es la más común de las displasias esqueléticas. Se trata de una enfermedad autosómica dominante con penetrancia completa. Esta enfermedad se debe a una mutación en el gen del receptor 3 del factor de crecimiento fibroblástico (FGFR3). El 90% o más de los casos se deben a mutaciones nuevas que se originan en las células germinales de padres sanos, asociada a una edad incrementada. Se ha calculado una frecuencia al nacimiento de 1:10.000 a 1:30.000. En la mayoría de los casos (97%) la mutación presente es la transición G1138A, en el dominio transmembranal de gen. En el resto se presenta la transversión en el mismo nucleótido, G1138C.
Objetivo. Detectar mutaciones del gen FGFR3 en un grupo de pacientes colombianos con acondroplasia.
Material y métodos. Estudiamos un grupo de 20 pacientes con diagnóstico clínico de acondroplasia. Se utilizó el método, ARMS-PCR (Amplification Refractory Mutation System - Polymerase Chain Reaction) que emplea dos pares primers diseñados específicamente para amplificar respectivamente los dos diferentes nucleótidos de una mutación puntual.
Resultados. 19 pacientes (95%), presentaron la mutación G1138A y un paciente presentó la mutación G1138C (5%).
Conclusión. No obstante la acondroplasia presentar un fenotipo considerado distinguible de otras displasias esqueléticas, algunas veces la hipocondroplasia, que se presenta por mutaciones en el mismo gen FGFR3, puede ser difícil de discriminar clínicamente, por lo que el análisis mutacional permite la correcta clasificación, así como de eventualmente otras displasias esqueléticas por mutaciones en otros genes.
Background. Achondroplasia is the most common skeletal dysplasia, mainly affecting tubular bones, vertebrae and skull. This is an autosomal dominant syndrome with complete penetrance, due to a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. Approximately 90% of the achondroplasia cases, are due to new mutations in the germ cells of otherwise normal fathers. Increased paternal age has been documented. It have been calculated a birth frequency of achondroplasia from 1:10.000 to 1:30.000. Most of the mutations causing achondroplasia (97%) is a transition G1138A in the transmenbranal domain of the gene. The rest is a transversion in the same nucleotide, G1138C. Rarely other mutations type are present.
Objective. To detect the mutations causing achondroplasia in a group of Colombian patients.
Materials and methods. 20 patients with clinical diagnosis of achondroplasia ware studied. The method, ARMS-PCR (Amplification Refractory Mutation System-Polymerase Chain Reaction) was used. This method employs two primers pairs to amplify, respectively.
Results. 19 patients (95%), presented the mutation G1138A and one patient presented the mutation G1138C. Conclusions. Not withstanding achondroplasia has a conspicuous phenotype, distinguishable from other skeletal dysplasias, sometimes hypochondroplasia, due to mutations in the same FGFR3 gen, could be difficult to discriminate. For that reason the mutational analysis is fundamental for the correct classification of these allelic forms. Or eventually, from other skeletal dysplasias due to other genes.
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Derechos de autor 2010 Revista de la Facultad de Medicina
Esta obra está bajo una licencia Creative Commons Reconocimiento 3.0 Unported.
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