Diagnóstico genético de duas famílias com casos de Acidose tubularrenal distal por meio de Whole-Exome Sequencing

• Ano de defesa: 2014
• Autor(a) principal: Paula Cristina de Barros Pereira
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais
• Palavras-chave em Português: Acidose tubular renal/genética; Acidose tubular renal/diagnóstico; Acidose tubular renal; Crescimento; Nefrocalcinose/diagnóstico; Genética; Criança; Adolescente; Transtornos do crescimento
• Link de acesso: https://hdl.handle.net/1843/BUBD-A8SL7F

renal tubular acidosis (RTA) or distal ATR type 1 comprises a heterogeneous group of disorders arising from dysfunction of the distal tubules, which can lead to a growth deficit, nephrocalcinosis, rickets and rarely chronic kidney disease. This tubulopathy may be transmitted either in an autosomal dominant manner and in autosomal recessive. The dominant form of the disease typically occurs in adolescence or adulthood, while the recessive variant develops predominantly in childhood. The aim of this study was to detect and characterize genetic asalterações present in two families, unrelated to patients with distal ATR atravésda methodology of whole-exome sequencing (WES). The family is 1 composed of a girl and her brother who had distal ATR and normal hearing, while the family had two twin sisters with distal ATR associated with sensorineural deafness. WES technique was performed on two pooled samples and to confirm the results was performed using the Sanger sequencing method. Two mutations were identified in ATP6VOA4 and ATP6V1B1 genes: a novel mutation in exon 13 of the gene ATP6V0A4 (c.1232G> T) and a mutation in exon 12 of the ATP6.V1B1 gene has been previously described in the literature (c.1149_1152insC). Our study indicates that the results obtained with whole-exome sequencing may be useful for the diagnosis and clinical management of patients distal ATR, especially because in addition to being a Mendelian disease is rare and complex inheritance. Our results confirm the value of whole-exome sequencing for the study of rare and complex diseases, allowing the identification of new and recurrent mutations. Furthermore, our study shows the applicability of this method to study the molecular Tubular renal disease. .