Academic Journal
Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity
| العنوان: | Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity |
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| المؤلفون: | Margutti, Ana Vitoria Barban, Silva, Wilson Araújo, Garcia, Daniel Fantozzi, de Molfetta, Greice Andreotti, Marques, Adriana Aparecida, Amorim, Tatiana, Prazeres, Vânia Mesquita Gadelha, Boy da Silva, Raquel Tavares, Miura, Irene Kazue, Seda Neto, João, Santos, Emerson de Santana, Santos, Mara Lúcia Schmitz Ferreira, Lourenço, Charles Marques, Tonon, Tássia, Sperb-Ludwig, Fernanda, de Souza, Carolina Fischinger Moura, Schwartz, Ida Vanessa Döederlein, Camelo, José Simon |
| المساهمون: | Nucleus of Research Support, Center for Integrative Systems Biology of University of São Paulo- Brazil, Conselho Nacional de Desenvolvimento Científico e Tecnológico |
| المصدر: | Orphanet Journal of Rare Diseases ; volume 15, issue 1 ; ISSN 1750-1172 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2020 |
| الوصف: | Background Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA , BCKDHB , DBT , and DLD genes. MSUD is predominantly caused by Variants in BCKDHA , BCKDHB , and DBT genes encoding the E1α, E1β, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA , BCKDHB , and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing. Results Eight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis. Conclusion Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s13023-020-01590-7 |
| DOI: | 10.1186/s13023-020-01590-7.pdf |
| DOI: | 10.1186/s13023-020-01590-7/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s13023-020-01590-7 http://link.springer.com/content/pdf/10.1186/s13023-020-01590-7.pdf http://link.springer.com/article/10.1186/s13023-020-01590-7/fulltext.html |
| Rights: | http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.278A35DB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s13023-020-01590-7 |
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