The Genetic Spectrum of Familial Hypertriglyceridemia in Oman.

Autor:	Al-Waili K; Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Al-Rasadi K; Medical Research Centre, College of Medicine and Health Sciences, Department of Biochemistry, Sultan Qaboos University, Muscat, Oman., Al-Bulushi M; Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Habais M; Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Al-Mujaini A; Department of Ophthalmology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Al-Yaarubi S; Department of Child Health, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman., Rimbert A; Nantes Université, CHU Nantes, CNRS, INSERM, L'institut du Thorax, Nantes, France., Zadjali R; Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Khaniabadi PM; Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Al-Barwani H; Sultan Qaboos Comprehensive Cancer Center, Muscat, Oman., Hasary S; Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Al-Dahmani ZM; Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Al-Badi H; Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Al-Maawali A; Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman., Zadjali F; Department of Clinical Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2022 May 20; Vol. 13, pp. 886182. Date of Electronic Publication: 2022 May 20 (Print Publication: 2022).
DOI:	10.3389/fgene.2022.886182
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor FS declared a past co-authorship with the authors KAL, KAR, HAB, FZ. (Copyright © 2022 Al-Waili, Al-Rasadi, Al-Bulushi, Habais, Al-Mujaini, Al-Yaarubi, Rimbert, Zadjali, Khaniabadi, Al-Barwani, Hasary, Al-Dahmani, Al-Badi, Al-Maawali and Zadjali.)
Databáze:	MEDLINE
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