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© 2021. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Molecular basis of various forms of maple syrup urine disease in Chilean patients
Author
Diana Ruffato Resende Campanholi 1   VIAFID ORCID Logo  ; Ana Vitoria Barban Margutti 1   VIAFID ORCID Logo  ; Silva, Wilson A, Jr 2   VIAFID ORCID Logo  ; Garcia, Daniel F 3   VIAFID ORCID Logo  ; Molfetta, Greice A 4   VIAFID ORCID Logo  ; Marques, Adriana A 5   VIAFID ORCID Logo  ; Ida Vanessa Döederlein Schwartz 6   VIAFID ORCID Logo  ; Cornejo, V 7   VIAFID ORCID Logo  ; Hamilton, Valerie 7   VIAFID ORCID Logo  ; Castro, Gabriela 7   VIAFID ORCID Logo  ; Fernanda Sperb‐Ludwig 8   VIAFID ORCID Logo  ; Borges, Ester S 9   VIAFID ORCID Logo  ; Camelo, José S, Jr 1   VIAFID ORCID Logo 

 Pediatrics Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil 
 Genetics Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Ribeirão Preto Regional Center of Hematology, National Institute of Science and Technology in Cell Therapy and Cell Therapy Center, Ribeirão Preto, Brazil; Clinical Hospital Genomic Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil 
 Genetics Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Ribeirão Preto Regional Center of Hematology, National Institute of Science and Technology in Cell Therapy and Cell Therapy Center, Ribeirão Preto, Brazil 
 Ribeirão Preto Regional Center of Hematology, National Institute of Science and Technology in Cell Therapy and Cell Therapy Center, Ribeirão Preto, Brazil; Clinical Hospital Genomic Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil 
 Ribeirão Preto Regional Center of Hematology, National Institute of Science and Technology in Cell Therapy and Cell Therapy Center, Ribeirão Preto, Brazil 
 Genetic Department, Porto Alegre Clinical Hospital, Porto Alegre, Brazil 
 Nutrition and Food Technology Institute, Chile University, Santiago, Chile 
 Genetic Department, Rio Grande do Sul Federal University, Porto Alegre, Brazil 
 School of Medicine, Federal University of São Carlos, São Carlos, Brazil 
Section
ORIGINAL ARTICLES
Publication year
2021
Publication date
May 2021
Publisher
John Wiley & Sons, Inc.
e-ISSN
23249269
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2535957602
Copyright
© 2021. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.