Anemia de Fanconi, Parte 2. Estrategia metodológica para el diagnóstico molecular en pacientes con anemia de Fanconi

  • Leda Torres Instituto Nacional de Pediatría
  • Ulises Juárez Instituto Nacional de Pediatría
  • Pedro Reyes Instituto Nacional de Pediatría
  • Sara Frías Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México

Resumen

La anemia de Fanconi es una enfermedad rara, se presenta en 1-5/millon de nacidos vivos. Los pacientes presentan a nivel celular inestabilidad cromosómica, que es la base para su diagnóstico y aunque clínicamente son heterogéneos, hay tres características generales: alteraciones del desarrollo físico, pancitopenia y alto riesgo a desarrollar cáncer. Presenta heterogeneidad genética, ya que se origina por variantes patogénicas en alguno de los 22 genes de la vía FA/BRCA, 20 de estos genes se heredan de manera autosómica recesiva, uno autosómica dominante y uno ligada al X. Debido a esta heterogeneidad, el diagnóstico molecular es complicado, por lo que se necesita una estrategia con varias metodologías. El primer abordaje es la detección de deleciones largas con el ensayo de amplificación de sondas dependiente de ligandos múltiples (MLPA) en los genes FANCA, FANCD2, FANCN/PALB2 y FANCB. Los casos no resueltos por  MLPA se canalizan a secuenciación de nueva generación, ya sea por panel dirigido (16 genes FANC), o por secuenciación del exoma completo, finalmente si todavía tenemos pacientes sin genotipo realizamos microarreglos de alta resolución, que constan de sondas a lo largo del genoma para detectar polimorfismos de un solo nucleótido y variaciones en el número de copias, para la búsqueda de grandes deleciones o duplicaciones en los genes FANC, así como para la detección de regiones con homocigosidad, con el propósito de encontrar alelos homocigotos. En este artículo, presentamos la estrategia detallada para realizar la genotipificación de los pacientes AF mexicanos, con un porcentaje de éxito del 80%.

Biografía del autor/a

Leda Torres, Instituto Nacional de Pediatría

Laboratorio de Citogenética

Ulises Juárez, Instituto Nacional de Pediatría

Laboratorio de Citogenética. Programa de Doctorado en Ciencias Biomédicas. Universidad Nacional Autónoma de México

 

 

Pedro Reyes, Instituto Nacional de Pediatría
Laboratorio de Citogenética. Programa de Doctorado en Ciencias Biomédicas. Universidad Nacional Autónoma de México
Sara Frías, Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México

Investigadora Titular, Laboratorio de Citogenética

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Publicado
2023-02-14
Cómo citar
Torres, L., Juárez, U., Reyes, P., & Frías, S. (2023). Anemia de Fanconi, Parte 2. Estrategia metodológica para el diagnóstico molecular en pacientes con anemia de Fanconi. Acta Pediátrica De México, 44(1), 29-55. https://doi.org/10.18233/APM44No1pp29-552548
Sección
Artículo de revisión