Introduction. Primary hypobetalipoproteinemia (pHBL) is amonogenic heterogeneous condition inherited as a dominant orrecessive trait characterized by total cholesterol (TC) and/or LDLcholesterol (LDL-C) and/or apolipoprotein B (APOB) levels belowthe 5th percentile of the reference population.Heterozygous APOB gene mutations are responsible for the majorityof the dominant pHBL causing the familial hypobetalipoproteinemia(FHBL). Loss-of-function mutations in the PCSK9 genealso cause FHBL. Familial combined hypolipidemia is a recentlydiscovered dyslipidemic phenotype characterized by low levels ofTC, triglycerides (TG), LDL-C, and high-density lipoprotein cholesterol(HDL-C). The genetic cause of familial combined hypolipidemiahas been attributed to mutations in the ANGPTL3 gene.methods and Results. In this report we describe a case of ayoung men with severe hypolipidemia characterized by low levelsof total cholesterol, triglycerides and HDL- (54 mg/dl, 26 mg/dl,17 mg/dl respectively). The proband’s mother and father showednormal plasma lipid values suggesting a recessive mode of inheritanceof the phenotype.In order to identify the molecular defects the analysis of MTPand SARA2 genes was carried out and no mutations were identifiedin both genes. We extended our analysis to the other knowngenes responsible for pHBL and we were able to identify in theANGPTL3 gene a novel splicing mutation (insT+3, IVS5) in homozigosity.Both parents were carriers of the same mutation inheterozygosity. InsT+3, IVS5 is predict to alter the correct splicingas predicted by in silico analysis.Conclusion. We describe a clinical case with severe hypolipidemiawith a recessive mode of inheritance carrying a novel mutationin Intron 5 of ANGPTL3.The mode of inheritance and the clinical implications of familialcombined hypolipidemia need to be further characterized.
Lingua originaleEnglish
Numero di pagine1
Stato di pubblicazionePublished - 2012


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