The Genetic Spectrum of Familial Hypertriglyceridemia in Oman

Khalid Al-Waili, Khalid Al-Rasadi, Muna Al-Bulushi, Mohammed Habais, Abdullah Al-Mujaini, Saif Al-Yaarubi, Antoine Rimbert, Razan Zadjali, Pegah Moradi Khaniabadi, Hamida Al-Barwani, Sana Hasary, Zayana M. Al-Dahmani, Hala Al-Badi, Almundher Al-Maawali, Fahad Zadjali*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Familial hypertriglyceridemia (F-HTG) is an autosomal disorder that causes severe elevation of serum triglyceride levels. It is caused by genetic alterations in LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes. The mutation spectrum of F-HTG in Arabic populations is limited. Here, we report the genetic spectrum of six families of F-HTG of Arab ancestry in Oman. Methods: six Omani families affected with triglyceride levels >11.2 mmol/L were included in this study. Ampli-Seq sequencing of the selected gene panels was performed. Whole-exome sequencing and copy number variant analysis were also performed in cases with negative exome results. Three novel pathogenic missense variants in the LPL gene were identified, p.M328T, p.H229L, and p.S286G, along with a novel splice variant c.1322+15T > G. The LPL p.H229L variant existed in double heterozygous mutation with the APOA5 gene p.V153M variant. One family had a homozygous mutation in the LMF1 gene (c.G107A; p.G36D) and a heterozygous mutation in the LPL gene (c.G106A; p.D36N). All affected subjects did not have a serum deficiency of LPL protein. Genetic analysis in one family did not show any pathogenic variants even after whole-exome sequencing. These novel LPL and APOA5 mutations are not reported in other ethnic groups. This suggests that patients with F-HTG in Oman have a founder effect and are genetically unique. This warrants further analysis of patients of F-HTG in the Middle East for preventative and counseling purposes to limit the spread of the disease in a population of high consanguinity.

Original languageEnglish
Article number886182
JournalFrontiers in Genetics
Volume13
DOIs
Publication statusPublished - May 20 2022

Keywords

  • familial hypertriglyceridemia
  • gene mutation
  • gene variant
  • lipoprotein lipase
  • LPL

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

Cite this