Clinical and molecular analysis of isovaleric acidemia patients in the United Arab Emirates reveals remarkable phenotypes and four novel mutations in the IVD gene

Jozef L. Hertecant, Imen Ben-Rebeh, Muhaned A. Marah, Thikra Abbas, Leila Ayadi, Salma Ben Salem, Fatma A. Al-Jasmi, Lihadh Al-Gazali, Said A. Al-Yahyaee, Bassam R. Ali

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism caused by deficiency of mitochondrial isovaleryl-CoA dehydrogenase (IVD). Accumulation of isovaleryl-CoA derivatives to toxic levels results in clinical symptoms of the disease. Here, we investigate the clinical and molecular features of Arab patients with IVA. Patients from five unrelated families were evaluated clinically and for defects in the IVD gene. Four novel mutations (p.F382fs, p.R392H, p.R395Q and p.E408K) have been identified with p.R395Q occurring in two families. In addition, molecular modeling of the identified missense mutations predicted their damaging effects on the protein and computational analysis of the p.F382fs mutation predicted the disruption of a 3' splicing site resulting in inactive or unstable gene product. Furthermore, we found an unusual case of a 17 years old female homozygous for the p.R392H mutation with no clinical symptoms. Our results illustrate a heterogeneous mutation spectrum and clinical presentation in the relatively small UAE population.

Original languageEnglish
Pages (from-to)671-676
Number of pages6
JournalEuropean Journal of Medical Genetics
Volume55
Issue number12
DOIs
Publication statusPublished - Dec 2012

Keywords

  • Isovaleric acidemia
  • Isovaleryl-CoA dehydrogenase
  • IVA
  • IVD

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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