| Texto completo | |
| Autor(es): |
Guaragna, Mara Sanches
[1]
;
de Brito Lutaif, Anna Cristina Gervasio
[2]
;
de Souza, Marcela Lopes
[1]
;
Maciel-Guerra, Andrea Trevas
[3]
;
Belangero, Vera Maria Santoro
[2, 4]
;
Guerra-Junior, Gil
[4, 5]
;
de Mello, Maricilda Palandi
[1]
Número total de Autores: 7
|
| Afiliação do(s) autor(es): | [1] Univ Estadual Campinas, Ctr Mol Biol & Genet Engn CBMEG, UNICAMP, Lab Human Mol Genet, Caixa Postal 6010, BR-13083875 Campinas, SP - Brazil
[2] Univ Estadual Campinas, UNICAMP, Sch Med Sci FCM, Integrated Ctr Pediat Nephrol CIN, Dept Pediat, Campinas - Brazil
[3] Univ Estadual Campinas, Sch Med Sci FCM, Dept Med Genet, Campinas, SP - Brazil
[4] Univ Estadual Campinas, Sch Med Sci FCM, Dept Pediat, Campinas, SP - Brazil
[5] Univ Estadual Campinas, Sch Med Sci FCM, Ctr Invest Pediat CIPED, Growth & Dev Lab, Campinas, SP - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Molecular Genetics and Genomics; v. 295, n. 1, p. 135-142, JAN 2020. |
| Citações Web of Science: | 0 |
| Resumo | |
High-throughput techniques such as whole-exome sequencing (WES) show promise for the identification of candidate genes that underlie Mendelian diseases such as nephrotic syndrome (NS). These techniques have enabled the identification of a proportion of the approximately 54 genes associated with NS. However, the main pitfall of using WES in clinical and research practice is the identification of multiple variants, which hampers interpretation during downstream analysis. One useful strategy is to evaluate the co-inheritance of rare variants in affected family members. Here, we performed WES of a patient with steroid-resistant NS (SRNS) and intermittent microhematuria. Currently, 15 years after kidney transplantation, this patient presents normal kidney function. The patient was found to be homozygous for a rare MYO1E stop-gain variant, and was heterozygous for rare variants in NS-associated genes, COL4A4, KANK1, LAMB2, ANLN, E2F3, and APOL1. We evaluated the presence or absence of these variants in both parents and 11 siblings, three of whom exhibited a milder phenotype of the kidney disease. Analysis of variant segregation in the family, indicated the MYO1E stop-gain variant as the putative causal variant underlying the kidney disease in the patient and two of her affected sisters. Two secondary variants in COL4A4-identified in some other affected family members-require further functional studies to determine whether they play a role in the development of microhematuria in affected family members. Our data illustrate the difficulties in distinguishing the causal pathogenic variants from incidental findings after WES-based variant analysis, especially in heterogenous genetic conditions, such as NS. (AU) | |
| Processo FAPESP: | 13/24088-4 - Implantação da Técnica de Sequenciamento de Exomas como Ferramenta de Pesquisa de Genes Relacionados com a Síndrome Nefrótica em Crianças e Adolescentes Brasileiros |
| Beneficiário: | Mara Sanches Guaragna |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 15/20502-6 - Estudo de Sequenciamento Completo de Exomas em Crianças e Adolescentes Brasileiros com Síndrome Nefrótica Córtico-Resistente |
| Beneficiário: | Maricilda Palandi de Mello |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |