En la página web de Decipher , puede consultarse un listado actualizado con todos los síndromes de microdelección y microduplicación.
Cada vez más síndromes de microduplicación y microdelección han ido identificándose a lo largo de los últimos años, con el uso creciente del aCGH en la investigación y la práctica clínica. Pueden clasificarse en función de varios criterios:
Criterio de recurrencia.
CNV recurrentes
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Están flanqueadas por regiones repetitivas cortas (LCR, low copy repeats), que frecuentemente dan lugar a puntos de ruptura por NAHR (non-allelic homologous recombination). Múltiples indivíduos no emparentados comparten los mismos puntos de ruptura. Suelen ser de novo. Se presentan con mayor frecuencia a la esperada por la tasa de mutación , por lo que son comparativamente más frecuentes.
CNV no recurrentes.
Suelen dar lugar a fenotipos más variables. Tienen puntos de ruptura distintos para cada individuo/familia, que se han producido de forma aleatoria a lo largo del genoma, dando lugar a la delección-duplicación cuando han intervenido los mecanismos de reparación (NHEJ, non homologous end-joining). Suelen ser heredadas, por lo que los puntos de ruptura serán característicos de cada familia. Existe una región compartida en todos los indivíduos con el mismo síndrome (SRO, smallest region of overlap), que alberga a los genes con repercusión fenotípica. Son menos frecuentes.
Criterio de penetrancia
CNV de penetrancia completa
Son síndromes “clásicos”, que se describieron a partir de la identificación del fenotipo clínico. Suelen nombrarse con un epónimo que alude al autor que los describió por primera vez. Suelen ser “de novo”, ya que la repercusión que producen sobre los indivíduos impide su reproducción. Coloca el ratón sobre la imagen para buscar algunos de los distintos síndromes de microdelección clásicos.
CNV de penetrancia incompleta
Suelen nombrarse con la región cromosómica a la que afectan. Son síndromes “nuevos”, identificados con más frecuencia a partir de la implementación de técnicas de diagnóstico molecular (aCGH).
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1.
Rosenfeld JA, Coe BP, Eichler EE, Cuckle H, Shaffer LG. Estimates of penetrance for recurrent pathogenic copy-number variations. Genetics in Medicine [Internet]. 2013 [cited 2018 Jul 16];15(6):478–81. Available from:
http://www.nature.com/articles/gim2012164
Tienen penetrancia incompleta, por lo que hay indivíduos portadores asintomáticos, y se produce con mayor frecuencia la transmisión familiar desde un indivíduo que no era consciente de su condición. Además, es más frecuente que se produzca la coexistencia de múltiples variantes patogénicas en el mismo indivíduo.
https://www.nejm.org/doi/full/10.1056/nejmoa1200395