RESUMO
A boy with a clinical history of pharmacologically resistant Dravet syndrome died suddenly after falling asleep. The autopsy concluded that the cause of death was sudden unexpected death in epilepsy (SUDEP). Postmortem molecular analysis of the SCN1A gene by multiplex ligation-dependent probe amplification (MLPA), high-resolution melting curve analysis (HRMCA), and sequencing revealed a frameshift duplication of adenosine at position 504. The incidence of this mutation is discussed as a potential cause of SUDEP.
Assuntos
Morte Súbita/epidemiologia , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/mortalidade , Malformações do Desenvolvimento Cortical/genética , Malformações do Desenvolvimento Cortical/mortalidade , Mutação/genética , Proteínas do Tecido Nervoso/genética , Canais de Sódio/genética , Causas de Morte , Criança , Epilepsias Mioclônicas/epidemiologia , Humanos , Masculino , Malformações do Desenvolvimento Cortical/epidemiologia , Canal de Sódio Disparado por Voltagem NAV1.1RESUMO
Mesomelic dysplasia is a severe shortening of forearms and forelegs, and is found in several distinct human syndromes. Here, we report the cloning of the breakpoints of a human t(2;8)(q31;p21) balanced translocation associated with mesomelic dysplasia of the upper limbs, as well as with vertebral defects. We show that this translocation does not disrupt any gene, hence it most likely exerts its deleterious effect by modifying gene regulation. The HOXD complex lies approximately 60 kb from the translocation breakpoint on chromosome 2. This cluster of genes has an important role in the development of both the vertebral column and the limbs. Only a few cases of mutations of these homeotic genes have been described so far in humans. However, gain- and loss-of-function of Hoxd genes in mice can induce mesomelic dysplasia-like phenotypes, suggesting that misexpression of HOXD genes may indeed be at the origin of this hereditary phenotype.
