Publication: Rendimiento de la técnica de "array" de hibridación genómica comparada aplicada al estudio de las discapacidades intelectuales y del desarrollo
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2016-09-19
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Universidad Complutense de Madrid
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Abstract
Las discapacidades intelectuales y del desarrollo tienen una prevalencia de entre 1 y 3% y suponen un impacto significativo en el funcionamiento del individuo que se prolonga a lo largo de toda su vida, así como elevados costes para los sistemas de salud y para la sociedad en su conjunto. En más del 50% de los casos la causa de la discapacidad intelectual y del desarrollo es desconocida, lo que impide indicar un tratamiento específico en caso de que lo hubiese, emitir un pronóstico, evitar exploraciones inútiles y llevar a cabo un consejo genético familiar y reproductivo. El desarrollo y la aplicación a la práctica clínica de técnicas moleculares de cribado genómico, en concreto del array de hibridación genómica comparada (array-CGH), que permite detectar pequeñas pérdidas y ganancias de material genético con una resolución de hasta miles de veces la correspondiente a un cariotipo convencional, han duplicado la tasa de diagnósticos de reordenamientos cromosómicos submicroscópicos como causa de discapacidad intelectual o del desarrollo, al detectarlos en alrededor del 15% de los casos. Justificación del trabajo Aunque hoy día se considera el array-CGH una prueba de primer nivel en el diagnóstico etiológico de las discapacidades intelectuales y las discapacidades del desarrollo sin causa aparente y sin una sospecha sindrómica clara, y a pesar de que su precio ha ido progresivamente disminuyendo, sigue siendo una técnica cara y de realización e interpretación costosa en términos de tiempo y personal. Por ese motivo, es importante establecer en nuestra población pediátrica el rendimiento de esta técnica en el estudio de las discapacidades intelectuales y del desarrollo. Demostrar en nuestra cohorte de pacientes un rendimiento al menos similar al reportado en otras poblaciones puede servir de argumento para salvar las limitaciones de acceso a este estudio que en la actualidad existen en nuestro país...
The incidence of intellectual disability and developmental impairment (IDDI) is between 1 and 3 %. They significantly impact functional ability over an individual's entire lifetime and are also extremely costly for healthcare systems and for society as a whole. The cause of IDDI is unknown in more than 50 % of cases, making administering a specific treatment, where one exists, advancing a prognosis, averting pointless testing, and genetic counselling for family reproductive planning unfeasible. The development of molecular genetic screening methods and their application to clinical practice has doubled the diagnosis rate for submicroscopic chromosomal rearrangements – found to be present in around 15 % of cases – as the cause of IDDI. More specifically, the use of array comparative genomic hybridization (array CGH) has enabled the detection of small losses and gains in genetic material at resolutions that can be up to thousands of times greater than those of conventional karyotyping. Rationale for this study While array CGH is today regarded as a first-tier test for diagnosing the aetiology of IDDI having no apparent cause or any clearly suspect syndrome, and even though its cost has been falling gradually, it continues to be an expensive technique, costly to carry out and interpret in terms of both the time and manpower required. For this reason it is important to ascertain the diagnostic yield of this method in studying IDDI in our paediatric population. Demonstrating levels of diagnostic yield in our patient cohort that are at least similar to those reported for other populations could provide an argument for obviating the restrictions on obtaining access to this method currently encountered in our country. Another interesting aspect is to assess whether our population contains subgroups that have specific clinical factors associated with positive study results...
The incidence of intellectual disability and developmental impairment (IDDI) is between 1 and 3 %. They significantly impact functional ability over an individual's entire lifetime and are also extremely costly for healthcare systems and for society as a whole. The cause of IDDI is unknown in more than 50 % of cases, making administering a specific treatment, where one exists, advancing a prognosis, averting pointless testing, and genetic counselling for family reproductive planning unfeasible. The development of molecular genetic screening methods and their application to clinical practice has doubled the diagnosis rate for submicroscopic chromosomal rearrangements – found to be present in around 15 % of cases – as the cause of IDDI. More specifically, the use of array comparative genomic hybridization (array CGH) has enabled the detection of small losses and gains in genetic material at resolutions that can be up to thousands of times greater than those of conventional karyotyping. Rationale for this study While array CGH is today regarded as a first-tier test for diagnosing the aetiology of IDDI having no apparent cause or any clearly suspect syndrome, and even though its cost has been falling gradually, it continues to be an expensive technique, costly to carry out and interpret in terms of both the time and manpower required. For this reason it is important to ascertain the diagnostic yield of this method in studying IDDI in our paediatric population. Demonstrating levels of diagnostic yield in our patient cohort that are at least similar to those reported for other populations could provide an argument for obviating the restrictions on obtaining access to this method currently encountered in our country. Another interesting aspect is to assess whether our population contains subgroups that have specific clinical factors associated with positive study results...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Pediatría, leída el 01/02/2016