Identification of a Novel Homozygous Mutation of the Bckdhb Gene in an Iranian Patient With Maple Syrup Disease Using Next-Generation Sequencing

Identification of a Novel Homozygous Mutation of the Bckdhb Gene in an Iranian Patient With Maple Syrup Disease Using Next-Generation Sequencing Publisher

Lashkarian MF¹ ; Salmani H²

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1. Department of Molecular Genetics, Islamic Azad University, Central Tehran Branch, Tehran, Iran
2. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Human Gene Published:2023

Abstract

Background: Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by decreased branched-chain alpha-keto acid dehydrogenase (BCKD) activity in human tissues. The BCKD enzyme is mostly active in the human body in the muscles and the brain; thus, genetic deficiency of the BCKD complex can result in neurological damage in patients. Deleterious mutations in BCKDHB, BCKDHA, DBT, and DLD genes have a significant impact on BCKD activity. Methods: In this study, we described a case of MSUD in a consanguineous Iranian family without a history of metabolic disorders. A 7-year-old boy was diagnosed 21 days after birth with lethargy, feeding problems, and vomiting. Plasma amino acid concentration and level of ammonia were measured. And then, whole-exome sequencing (WES) 100× was used to identify causative mutation along with some bioinformatics analysis. Results: A novel pathogenic homozygous mutation, c.552_553insA; P185Tfs*17, was detected in the BCKDHB gene's exon5. This variant was predicted as a pathogenic mutation using bioinformatics tools including Mutationtaster, Fathmm-mkl, Provean, DEOGEN2, SNPs&GO, PhyloP, and PhastCons. This mutation leads to a truncated protein in which conserved regions are lost. Besides, the variant is completely co-segregated with the disease in this family. Conclusion: A novel pathogenic mutation c.552_553insA in the BCKDHB gene related to MSUD was diagnosed in an Iranian family. This finding from the present study can be efficient in upgrading mutation databases and recognizing MSUD causes. © 2023 Elsevier B.V.

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Shahriar Nafissi (2)

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Style	Citing Format
MLA	Lashkarian MF, Salmani H. "Identification of a Novel Homozygous Mutation of the Bckdhb Gene in an Iranian Patient With Maple Syrup Disease Using Next-Generation Sequencing." Human Gene, vol. 36, no. , 2023, pp. -.
APA	Lashkarian MF, Salmani H (2023). Identification of a Novel Homozygous Mutation of the Bckdhb Gene in an Iranian Patient With Maple Syrup Disease Using Next-Generation Sequencing. Human Gene, 36(), -.
Chicago	Lashkarian MF, Salmani H. "Identification of a Novel Homozygous Mutation of the Bckdhb Gene in an Iranian Patient With Maple Syrup Disease Using Next-Generation Sequencing." Human Gene 36, no. (2023): -.
Harvard	Lashkarian MF, Salmani H (2023) 'Identification of a Novel Homozygous Mutation of the Bckdhb Gene in an Iranian Patient With Maple Syrup Disease Using Next-Generation Sequencing', Human Gene, 36(), pp. -.
Vancouver	Lashkarian MF, Salmani H. Identification of a Novel Homozygous Mutation of the Bckdhb Gene in an Iranian Patient With Maple Syrup Disease Using Next-Generation Sequencing. Human Gene. 2023;36():-.
BibTex	@article{ author = {Lashkarian MF and Salmani H}, title = {Identification of a Novel Homozygous Mutation of the Bckdhb Gene in an Iranian Patient With Maple Syrup Disease Using Next-Generation Sequencing}, journal = {Human Gene}, volume = {36}, number = {}, pages = {-}, year = {2023} }
RIS	TY - JOUR AU - Lashkarian MF AU - Salmani H TI - Identification of a Novel Homozygous Mutation of the Bckdhb Gene in an Iranian Patient With Maple Syrup Disease Using Next-Generation Sequencing JO - Human Gene VL - 36 IS - SP - EP - PY - 2023 ER -

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