International Journal of Genetics and Molecular Biology
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Article Number - 99935A359585


Vol.8(3), pp. 11-17 , July 2016
DOI: 10.5897/IJGMB2016.0126
ISSN: 2006-9863



Full Length Research Paper

Recurrent mutation in the HMGCL gene in a family segregating HMG-CoA lyase deficiency



Essa Alharby
  • Essa Alharby
  • Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawwarah, Saudi Arabia.
  • Google Scholar
Omhani Malibari
  • Omhani Malibari
  • Department of Metabolic Diseases, King Abdulla Medical City-Madinah Maternity and Children Hospital, Almadinah Almunawwarah, Saudi Arabia.
  • Google Scholar
Hamad S. Al-Otaibi
  • Hamad S. Al-Otaibi
  • College of Applied Medical Science, Taibah University Almadinah Almunawwarah, Saudi Arabia.
  • Google Scholar
Muhammad Saud
  • Muhammad Saud
  • College of Applied Medical Science, Taibah University Almadinah Almunawwarah, Saudi Arabia.
  • Google Scholar
Ghadeer Al-Harbi
  • Ghadeer Al-Harbi
  • Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawwarah, Saudi Arabia.
  • Google Scholar
Mohammad I. Samman
  • Mohammad I. Samman
  • Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawwarah, Saudi Arabia.
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Sulman Basit
  • Sulman Basit
  • Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawwarah, Saudi Arabia.
  • Google Scholar







 Received: 12 April 2016  Accepted: 21 June 2016  Published: 31 July 2016

Copyright © 2016 Author(s) retain the copyright of this article.
This article is published under the terms of the Creative Commons Attribution License 4.0


The gene HMGCL encodes 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase. Mutations in HMG-CoA lyase cause HMG-CoA lyase deficiency (HMGCLD), which is an autosomal recessive congenital disorder of metabolism. This study was designed to detect mutation in the 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) gene in a Saudi family segregating HMG-CoA lyase deficiency (HMGCLD).Methods: Clinical and molecular genetic analysis of a Saudi family with five individuals affected with HMGCLD was performed by GC-MS, tandem MS and sequencing. This study was conducted in the Centre for Genetics and Inherited Diseases, Taibah University Almadinah Almunawwarah, Saudi Arabia from September 2015 to February 2016. Sanger sequencing of the entire coding region and the intron-exon junctions of the HMGCL gene identified a recurrent missense mutation in exon 2. This mutation (c.122G>A) causes a substitution of a highly conserved amino acid Arginine to a Glutamine residue at position 41 (p.Arg41Gln). This is the most frequent mutation found in the HMGCL gene in Saudi population and might have occurred due to a founder effect. Multiple in silico software predicted this mutation as disease-causing. Moreover, to determine the protein stability upon change in amino acid various tools including SDM, I-Mutant, mCSM and DUET were used and found that the mutation, identified in this family, is protein destabilizing. An extensive literature review was performed and all mutations reported to date in the HMGCL gene were identified and listed.

 

Key words: HMGCL gene, 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMG-CoA lyase) deficiency, homozygous mutation, protein stability.

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APA Alharby, E., Malibari, O., Al-Otaibi, H. S., Saud, M., Al-Harbi, G., Samman, M. I., & Basit, S. (2016). Recurrent mutation in the HMGCL gene in a family segregating HMG-CoA lyase deficiency. International Journal of Genetics and Molecular Biology, 8(3), 11-17.
Chicago Essa Alharby, Omhani Malibari, Hamad S. Al-Otaibi, Muhammad Saud, Ghadeer Al-Harbi, Mohammad I. Samman, and Sulman Basit. "Recurrent mutation in the HMGCL gene in a family segregating HMG-CoA lyase deficiency." International Journal of Genetics and Molecular Biology 8, no. 3 (2016): 11-17.
MLA Essa Alharby, et al. "Recurrent mutation in the HMGCL gene in a family segregating HMG-CoA lyase deficiency." International Journal of Genetics and Molecular Biology 8.3 (2016): 11-17.
   
DOI 10.5897/IJGMB2016.0126
URL http://academicjournals.org/journal/IJGMB/article-abstract/99935A359585

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