RESUMEN
Lafora progressive myoclonus epilepsy is characterized by pathognomonic endoplasmic reticulum (ER)-associated polyglucosan accumulations. We previously discovered that mutations in EPM2A cause Lafora disease. Here, we identify a second gene associated with this disease, NHLRC1 (also called EPM2B), which encodes malin, a putative E3 ubiquitin ligase with a RING finger domain and six NHL motifs. Laforin and malin colocalize to the ER, suggesting they operate in a related pathway protecting against polyglucosan accumulation and epilepsy.
Asunto(s)
Proteínas Portadoras/genética , Mutación , Epilepsias Mioclónicas Progresivas/genética , Proteínas Tirosina Fosfatasas/genética , Secuencia de Bases , Estudios de Cohortes , Femenino , Homocigoto , Humanos , Enfermedad de Lafora/genética , Masculino , Datos de Secuencia Molecular , Epilepsias Mioclónicas Progresivas/enzimología , Linaje , Proteínas Tirosina Fosfatasas no Receptoras , Eliminación de Secuencia , Ubiquitina-Proteína LigasasRESUMEN
DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.