The Genetic Spectrum of Familial Hypertriglyceridemia in Oman

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 heterozygousmutation
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.