Molecular basis of various forms of maple syrup urine disease in Chilean patients
| Autor: | Adriana Aparecida Marques, Gabriela Castro, Greice Andreotti de Molfetta, Daniel F. Garcia, Ester Simon Borges, Valerie Hamilton, Wilson A. Silva, Ida Vanessa Doederlein Schwartz, Ana Vitoria Barban Margutti, Verónica Cornejo, José Simon Camelo, Fernanda Sperb-Ludwig, Diana Ruffato Resende Campanholi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities BCKDHB isoleucine BCKDHA branched‐chain amino acids inborn errors of metabolism 030105 genetics & heredity Biology QH426-470 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) 03 medical and health sciences Genotype-phenotype distinction valine medicine Genetics Humans Genetic Testing Chile DOENÇA DA URINA DE XAROPE DE BORDO Child Molecular Biology Gene Genetics (clinical) Dihydrolipoamide Dehydrogenase Newborn screening Genetic heterogeneity Maple syrup urine disease Point mutation nutritional and metabolic diseases Original Articles medicine.disease maple syrup urine disease 030104 developmental biology Mutation Original Article leucine Acyltransferases |
| Zdroj: | Molecular Genetics & Genomic Medicine Molecular Genetics & Genomic Medicine, Vol 9, Iss 5, Pp n/a-n/a (2021) Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 2324-9269 |
| Popis: | Background Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched‐chain α‐keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes which encode the E1α, E1β, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes and to describe their impact on the phenotypic heterogeneity of these patients. Methods This manuscript describes a cross‐sectional study of 18 MSUD patients carried out using PCR and DNA sequencing. Results Four novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously. There were no correlations between the genotype and phenotype of the patients. Conclusion If MSUD is diagnosed earlier, with a newborn screening approach, it might be possible to establish genotype‐phenotype relationships more efficiently. This manuscript describes a cross‐sectional study of 18 MSUD patients carried out using PCR and DNA sequencing. Four novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously. There were no correlations between the genotype and phenotype of the patients. |
| Databáze: | OpenAIRE |
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