Pathogenic Homozygous Mutations in the DBT Gene (c.1174A>C) Result in Maple Syrup Urine Disease in a rs12021720 Carrier

Morteza Alijanpour; Omid Jazayeri; Shima Soleimani Amiri; Erwin Brosens

doi:10.1093/labmed/lmac034

Pathogenic Homozygous Mutations in the DBT Gene (c.1174A>C) Result in Maple Syrup Urine Disease in a rs12021720 Carrier

Morteza Alijanpour, Omid Jazayeri^*, Shima Soleimani Amiri, Erwin Brosens

^*Corresponding author for this work

Clinical Genetics

Research output: Contribution to journal › Article › Academic › peer-review

4 Citations (Scopus)

Abstract

OBJECTIVE: Maple syrup urine disease (MSUD; OMIM #248600) is an autosomal recessive metabolic disorder in the catabolism of branched-chain amino acids (leucine, isoleucine, and valine) and may be lethal if untreated in affected newborns. METHODS: Single-nucleotide polymorphism haplotyping and Sanger sequencing of BCKDHA, BCKDHB, and DBT genes were performed in a cohort of 10 MSUD patients. RESULTS: We identified a 16.6 Mb homozygous region harboring the DBT gene in an Iranian girl presenting with MSUD. Sanger sequencing revealed a pathogenic homozygous variant (NM_001918.3: c.1174A > C) in the DBT gene. We further found a controversial variant (rs12021720: c.1150 A > G) in the DBT gene. This substitution (p.Ser384Gly) is highly debated in literature. Bioinformatics and cosegregation analysis, along with identifying the real pathogenic variants (c.1174 A > C), lead to terminate these various interpretations of c.1150 A > G variant. CONCLUSION: Our study introduced c.1150 A > G as a polymorphic variant, which is informative for variant databases and also helpful in molecular diagnosis.

Original language	English
Pages (from-to)	596-601
Number of pages	6
Journal	Laboratory Medicine
Volume	53
Issue number	6
DOIs	https://doi.org/10.1093/labmed/lmac034
Publication status	Published - 1 Nov 2022

Bibliographical note

Funding:
This work was a joint project and supported by the Babol University of
Medical Science, University of Mazandaran, and Babol Razi Pathobiology
and Genetic Center Diagnostic Laboratory.

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: [email protected].

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10.1093/labmed/lmac034

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title = "Pathogenic Homozygous Mutations in the DBT Gene (c.1174A>C) Result in Maple Syrup Urine Disease in a rs12021720 Carrier",

abstract = "OBJECTIVE: Maple syrup urine disease (MSUD; OMIM #248600) is an autosomal recessive metabolic disorder in the catabolism of branched-chain amino acids (leucine, isoleucine, and valine) and may be lethal if untreated in affected newborns. METHODS: Single-nucleotide polymorphism haplotyping and Sanger sequencing of BCKDHA, BCKDHB, and DBT genes were performed in a cohort of 10 MSUD patients. RESULTS: We identified a 16.6 Mb homozygous region harboring the DBT gene in an Iranian girl presenting with MSUD. Sanger sequencing revealed a pathogenic homozygous variant (NM_001918.3: c.1174A > C) in the DBT gene. We further found a controversial variant (rs12021720: c.1150 A > G) in the DBT gene. This substitution (p.Ser384Gly) is highly debated in literature. Bioinformatics and cosegregation analysis, along with identifying the real pathogenic variants (c.1174 A > C), lead to terminate these various interpretations of c.1150 A > G variant. CONCLUSION: Our study introduced c.1150 A > G as a polymorphic variant, which is informative for variant databases and also helpful in molecular diagnosis.",

author = "Morteza Alijanpour and Omid Jazayeri and {Soleimani Amiri}, Shima and Erwin Brosens",

note = "Funding: This work was a joint project and supported by the Babol University of Medical Science, University of Mazandaran, and Babol Razi Pathobiology and Genetic Center Diagnostic Laboratory. Publisher Copyright: {\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: [email protected].",

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doi = "10.1093/labmed/lmac034",

language = "English",

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AU - Alijanpour, Morteza

AU - Jazayeri, Omid

AU - Soleimani Amiri, Shima

AU - Brosens, Erwin

N1 - Funding: This work was a joint project and supported by the Babol University of Medical Science, University of Mazandaran, and Babol Razi Pathobiology and Genetic Center Diagnostic Laboratory. Publisher Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: [email protected].

PY - 2022/11/1

Y1 - 2022/11/1

N2 - OBJECTIVE: Maple syrup urine disease (MSUD; OMIM #248600) is an autosomal recessive metabolic disorder in the catabolism of branched-chain amino acids (leucine, isoleucine, and valine) and may be lethal if untreated in affected newborns. METHODS: Single-nucleotide polymorphism haplotyping and Sanger sequencing of BCKDHA, BCKDHB, and DBT genes were performed in a cohort of 10 MSUD patients. RESULTS: We identified a 16.6 Mb homozygous region harboring the DBT gene in an Iranian girl presenting with MSUD. Sanger sequencing revealed a pathogenic homozygous variant (NM_001918.3: c.1174A > C) in the DBT gene. We further found a controversial variant (rs12021720: c.1150 A > G) in the DBT gene. This substitution (p.Ser384Gly) is highly debated in literature. Bioinformatics and cosegregation analysis, along with identifying the real pathogenic variants (c.1174 A > C), lead to terminate these various interpretations of c.1150 A > G variant. CONCLUSION: Our study introduced c.1150 A > G as a polymorphic variant, which is informative for variant databases and also helpful in molecular diagnosis.

AB - OBJECTIVE: Maple syrup urine disease (MSUD; OMIM #248600) is an autosomal recessive metabolic disorder in the catabolism of branched-chain amino acids (leucine, isoleucine, and valine) and may be lethal if untreated in affected newborns. METHODS: Single-nucleotide polymorphism haplotyping and Sanger sequencing of BCKDHA, BCKDHB, and DBT genes were performed in a cohort of 10 MSUD patients. RESULTS: We identified a 16.6 Mb homozygous region harboring the DBT gene in an Iranian girl presenting with MSUD. Sanger sequencing revealed a pathogenic homozygous variant (NM_001918.3: c.1174A > C) in the DBT gene. We further found a controversial variant (rs12021720: c.1150 A > G) in the DBT gene. This substitution (p.Ser384Gly) is highly debated in literature. Bioinformatics and cosegregation analysis, along with identifying the real pathogenic variants (c.1174 A > C), lead to terminate these various interpretations of c.1150 A > G variant. CONCLUSION: Our study introduced c.1150 A > G as a polymorphic variant, which is informative for variant databases and also helpful in molecular diagnosis.

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Pathogenic Homozygous Mutations in the DBT Gene (c.1174A>C) Result in Maple Syrup Urine Disease in a rs12021720 Carrier

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