Novel CREB3L3 Nonsense Mutation in a Family With Dominant Hypertriglyceridemia

Angelo Baldassare Cefalu', Vincenza Valenti, Maria Donata Panno, Rossella Spina, Antonina Giammanco, Carlo Maria Barbagallo, Maurizio Averna, Valeria Ingrassia, Vincenza Valenti, Rossella Spina, Angelo B. Cefalu, Valeria Ingrassia, Davide Noto, Maurizio R. Averna, Antonina Ganci, Davide Noto

Research output: Contribution to journalArticle

9 Citations (Scopus)


OBJECTIVE—: Cyclic AMP responsive element–binding protein 3–like 3 (CREB3L3) is a novel candidate gene for dominant hypertriglyceridemia. To date, only 4 kindred with dominant hypertriglyceridemia have been found to be carriers of 2 nonsense mutations in CREB3L3 gene (245fs and W46X). We investigated a family in which hypertriglyceridemia displayed an autosomal dominant pattern of inheritance. APPROACH AND RESULTS—: The proband was a 49-year-old woman with high plasma triglycerides (≤1300 mg/dL; 14.68 mmol/L). Her father had a history of moderate hypertriglyceridemia, and her 51-year-old brother had triglycerides levels as high as 1600 mg/dL (18.06 mmol/L). To identify the causal mutation in this family, we analyzed the candidate genes of recessive and dominant forms of primary hypertriglyceridemia by direct sequencing. The sequencing of CREB3L3 gene led to the discovery of a novel minute frame shift mutation in exon 3 of CREB3L3 gene, predicted to result in the formation of a truncated protein devoid of function (c.359delG–p.K120fsX20). Heterozygosity for the c.359delG mutation resulted in a severe phenotype in the proband, and her brother with a late in life expression and a good response to diet and a hypotriglyceridemic treatment. The same mutation was detected in a 13-year-old daughter who to date is normotriglyceridemic. CONCLUSIONS—: We have identified a novel pathogenic mutation in CREB3L3 gene in a family with dominant hypertriglyceridemia with a variable pattern of penetrance.
Original languageEnglish
Pages (from-to)2694-2699
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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