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O gene CLCN4 codifica a prote\u00edna CIC-4, que \u00e9 um trocador de 2Cl-\/H+ expresso em compartimentos intracelulares em uma ampla variedade de tecidos, mas com destaque para o c\u00e9rebro e o m\u00fasculo esquel\u00e9tico. Acredita-se que a CIC-4 seja expressa dentro das c\u00e9lulas nos endossomos e possivelmente no ret\u00edculo endoplasm\u00e1tico, e que esteja envolvida na homeostase i\u00f4nica dos endossomos e no tr\u00e1fico intracelular. Uma fun\u00e7\u00e3o da CIC-4 na diferencia\u00e7\u00e3o neuronal foi sugerida por estudos em camundongos: neur\u00f4nios do hipocampo de camundongos com nocaute da Clcn4 e neur\u00f4nios do tipo selvagem submetidos ao nocaute da Clcn4 mediado por shRNA demonstram uma redu\u00e7\u00e3o no n\u00famero total de ramos dendr\u00edticos por neur\u00f4nio. No entanto, a fisiopatologia do dist\u00farbio relacionado ao CLCN4 em humanos n\u00e3o \u00e9 totalmente compreendida. <\/p>\n
O espectro de muta\u00e7\u00f5es inclui frameshift, missense e variantes de locais de emenda, al\u00e9m de microdele\u00e7\u00f5es cromoss\u00f4micas.
As variantes patog\u00eanicas de missense se agrupam dentro dos dom\u00ednios helicoidais trans ou intermembrana da prote\u00edna, ou no dom\u00ednio da cistationina-\u03b2-sintase (CBS), que se acredita ser importante para a abertura do antiporte. Todas as variantes missense conhecidas at\u00e9 o momento que se agrupam nessas regi\u00f5es demonstraram ter um efeito funcional em estudos eletrofisiol\u00f3gicos quando expressas heterologicamente em o\u00f3citos de Xenopus laevis. Todas as mulheres afetadas conhecidas at\u00e9 o momento t\u00eam uma variante missense no CLCN4: portadoras heterozigotas em fam\u00edlias com variantes de perda de fun\u00e7\u00e3o previstas t\u00eam fen\u00f3tipos essencialmente normais. <\/p>\n
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O gene CLCN4 codifica a prote\u00edna CIC-4, que \u00e9 um trocador de 2Cl-\/H+ expresso em compartimentos intracelulares em uma ampla variedade de tecidos, mas com destaque para o c\u00e9rebro e o m\u00fasculo esquel\u00e9tico. Acredita-se que a ClC-4 seja expressa dentro das c\u00e9lulas nos endossomos e possivelmente no ret\u00edculo endoplasm\u00e1tico, e que esteja envolvida na homeostase i\u00f4nica dos endossomos e no tr\u00e1fico intracelular. <\/p>\n","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"class_list":["post-7536","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/cureclcn4.org\/pt-br\/wp-json\/wp\/v2\/pages\/7536","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cureclcn4.org\/pt-br\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/cureclcn4.org\/pt-br\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/cureclcn4.org\/pt-br\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/cureclcn4.org\/pt-br\/wp-json\/wp\/v2\/comments?post=7536"}],"version-history":[{"count":2,"href":"https:\/\/cureclcn4.org\/pt-br\/wp-json\/wp\/v2\/pages\/7536\/revisions"}],"predecessor-version":[{"id":7538,"href":"https:\/\/cureclcn4.org\/pt-br\/wp-json\/wp\/v2\/pages\/7536\/revisions\/7538"}],"wp:attachment":[{"href":"https:\/\/cureclcn4.org\/pt-br\/wp-json\/wp\/v2\/media?parent=7536"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}