TY - JOUR
T1 - Novel CREB3L3 Nonsense Mutation in a Family With Dominant Hypertriglyceridemia
AU - Valenti, Vincenza
AU - Giammanco, Antonina
AU - Averna, Maurizio
AU - Cefalu', Angelo Baldassare
AU - Panno, Maria Donata
AU - Ingrassia, Valeria
AU - Barbagallo, Carlo Maria
AU - Noto, Davide
AU - Spina, Rossella
AU - Valenti, Vincenza
AU - Spina, Rossella
AU - Cefalu, Angelo B.
AU - Ingrassia, Valeria
AU - Noto, Davide
AU - Averna, Maurizio R.
AU - Ganci, Antonina
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10447/151391
UR - http://atvb.ahajournals.org/
M3 - Article
VL - 35
SP - 2694
EP - 2699
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
ER -