See the published version of this preprint at Orphanet Journal of Rare Diseases.
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José Simon Camelo Junior
Universidade de Sao Paulo
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4555-7633
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This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
inborn errors of metabolism, maple syrup urine disease, branched-chain amino acids, valine, leucine, isoleucine
This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile1.pdf
File name: Additional file 1 File format: .docx Title of data: Primers sequences, PCR conditions and amplified fragment sizes of the BCKDHA gene. Description of data: Primer location, primer sequences, Annealing Temperature and amplified fragment sizes (amplicon size) of the BCKDHA gene.
- Additionalfile2.pdf
File name: Additional file 2 File format: .docx Title of data: Primers sequences, PCR conditions and amplified fragment sizes of the BCKDHB gene. Description of data: Primer location, primer sequences, Annealing Temperature and amplified fragment sizes (amplicon size) of the BCKDHB gene.
- Additionalfile3.pdf
File name: Additional file 3 File format: .docx Title of data: Primers sequences, PCR conditions and amplified fragment sizes of the DBT gene. Description of data: Primer location, primer sequences, Annealing Temperature and amplified fragment sizes (amplicon size) of the DBT gene.
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CURRENT STATUS: Published
View the published article at Orphanet Journal of Rare Diseases.
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Posted 20 Oct, 2020
No community comments so far
Editorial decision: Accept
On 15 Oct, 2020
Editor assigned
On 11 Oct, 2020
Submission checks complete
On 10 Oct, 2020
Editor invited
On 10 Oct, 2020
No comments provided
Editorial decision: Minor revision
On 23 Sep, 2020
Review #1 received
Received 30 Aug, 2020
Reviewers invited
Invitations sent on 19 Aug, 2020
Reviewer #1 agreed
On 19 Aug, 2020
Editor assigned
On 16 Aug, 2020
Submission checks complete
On 15 Aug, 2020
Editor invited
On 15 Aug, 2020
No comments provided
Editorial decision: Minor revision
On 26 Jul, 2020
Review #1 received
Received 22 Jun, 2020
Reviewer #1 agreed
On 21 May, 2020
Reviewers invited
Invitations sent on 24 Apr, 2020
Editor assigned
On 02 Mar, 2020
Submission checks complete
On 01 Mar, 2020
Editor invited
On 01 Mar, 2020
No comments provided
Editorial decision: Minor revision
On 26 Jan, 2020
Review #2 received
Received 25 Jan, 2020
Reviewer #2 agreed
On 08 Jan, 2020
Review #1 received
Received 31 Dec, 2019
Reviewer #1 agreed
On 16 Dec, 2019
Reviewers invited
Invitations sent on 21 Nov, 2019
Editor assigned
On 19 Nov, 2019
First submitted
On 18 Nov, 2019
Submission checks complete
On 18 Nov, 2019
Editor invited
On 18 Nov, 2019
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at Orphanet Journal of Rare Diseases.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
José Simon Camelo Junior
Universidade de Sao Paulo
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4555-7633
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Orphanet Journal of Rare Diseases.
Version 4
Posted 20 Oct, 2020
No community comments so far
Editorial decision: Accept
On 15 Oct, 2020
Editor assigned
On 11 Oct, 2020
Submission checks complete
On 10 Oct, 2020
Editor invited
On 10 Oct, 2020
No comments provided
Editorial decision: Minor revision
On 23 Sep, 2020
Review #1 received
Received 30 Aug, 2020
Reviewers invited
Invitations sent on 19 Aug, 2020
Reviewer #1 agreed
On 19 Aug, 2020
Editor assigned
On 16 Aug, 2020
Submission checks complete
On 15 Aug, 2020
Editor invited
On 15 Aug, 2020
No comments provided
Editorial decision: Minor revision
On 26 Jul, 2020
Review #1 received
Received 22 Jun, 2020
Reviewer #1 agreed
On 21 May, 2020
Reviewers invited
Invitations sent on 24 Apr, 2020
Editor assigned
On 02 Mar, 2020
Submission checks complete
On 01 Mar, 2020
Editor invited
On 01 Mar, 2020
No comments provided
Editorial decision: Minor revision
On 26 Jan, 2020
Review #2 received
Received 25 Jan, 2020
Reviewer #2 agreed
On 08 Jan, 2020
Review #1 received
Received 31 Dec, 2019
Reviewer #1 agreed
On 16 Dec, 2019
Reviewers invited
Invitations sent on 21 Nov, 2019
Editor assigned
On 19 Nov, 2019
First submitted
On 18 Nov, 2019
Submission checks complete
On 18 Nov, 2019
Editor invited
On 18 Nov, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Orphanet Journal of Rare Diseases.
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.
This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile1.pdf
File name: Additional file 1 File format: .docx Title of data: Primers sequences, PCR conditions and amplified fragment sizes of the BCKDHA gene. Description of data: Primer location, primer sequences, Annealing Temperature and amplified fragment sizes (amplicon size) of the BCKDHA gene.
- Additionalfile2.pdf
File name: Additional file 2 File format: .docx Title of data: Primers sequences, PCR conditions and amplified fragment sizes of the BCKDHB gene. Description of data: Primer location, primer sequences, Annealing Temperature and amplified fragment sizes (amplicon size) of the BCKDHB gene.
- Additionalfile3.pdf
File name: Additional file 3 File format: .docx Title of data: Primers sequences, PCR conditions and amplified fragment sizes of the DBT gene. Description of data: Primer location, primer sequences, Annealing Temperature and amplified fragment sizes (amplicon size) of the DBT gene.
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