title: Novel CREB3L3 Nonsense Mutation in a Family With Dominant Hypertriglyceridemia.
abstract: 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.
  
  
  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 occurring later in life in the proband and her brother 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.
authors.affiliation: From the Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy (A.B.C., R.S., D.N., V.I., A. Giammanco, M.D.P., A. Ganci, C.M.B., M.R.A.); and Molecular Biology Diagnostic Laboratory, Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP "Paolo Giaccone", Palermo, Italy (A.B.C., R.S., D.N., V.V., V.I., M.R.A.).
authors.forename: Angelo B
authors.initials: AB
authors.lastname: Cefalù
authors.affiliation: From the Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy (A.B.C., R.S., D.N., V.I., A. Giammanco, M.D.P., A. Ganci, C.M.B., M.R.A.); and Molecular Biology Diagnostic Laboratory, Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP "Paolo Giaccone", Palermo, Italy (A.B.C., R.S., D.N., V.V., V.I., M.R.A.).
authors.forename: Rossella
authors.initials: R
authors.lastname: Spina
authors.affiliation: From the Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy (A.B.C., R.S., D.N., V.I., A. Giammanco, M.D.P., A. Ganci, C.M.B., M.R.A.); and Molecular Biology Diagnostic Laboratory, Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP "Paolo Giaccone", Palermo, Italy (A.B.C., R.S., D.N., V.V., V.I., M.R.A.).
authors.forename: Davide
authors.initials: D
authors.lastname: Noto
authors.affiliation: From the Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy (A.B.C., R.S., D.N., V.I., A. Giammanco, M.D.P., A. Ganci, C.M.B., M.R.A.); and Molecular Biology Diagnostic Laboratory, Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP "Paolo Giaccone", Palermo, Italy (A.B.C., R.S., D.N., V.V., V.I., M.R.A.).
authors.forename: Vincenza
authors.initials: V
authors.lastname: Valenti
authors.affiliation: From the Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy (A.B.C., R.S., D.N., V.I., A. Giammanco, M.D.P., A. Ganci, C.M.B., M.R.A.); and Molecular Biology Diagnostic Laboratory, Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP "Paolo Giaccone", Palermo, Italy (A.B.C., R.S., D.N., V.V., V.I., M.R.A.).
authors.forename: Valeria
authors.initials: V
authors.lastname: Ingrassia
authors.affiliation: From the Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy (A.B.C., R.S., D.N., V.I., A. Giammanco, M.D.P., A. Ganci, C.M.B., M.R.A.); and Molecular Biology Diagnostic Laboratory, Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP "Paolo Giaccone", Palermo, Italy (A.B.C., R.S., D.N., V.V., V.I., M.R.A.).
authors.forename: Antonina
authors.initials: A
authors.lastname: Giammanco
authors.affiliation: From the Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy (A.B.C., R.S., D.N., V.I., A. Giammanco, M.D.P., A. Ganci, C.M.B., M.R.A.); and Molecular Biology Diagnostic Laboratory, Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP "Paolo Giaccone", Palermo, Italy (A.B.C., R.S., D.N., V.V., V.I., M.R.A.).
authors.forename: Maria D
authors.initials: MD
authors.lastname: Panno
authors.affiliation: From the Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy (A.B.C., R.S., D.N., V.I., A. Giammanco, M.D.P., A. Ganci, C.M.B., M.R.A.); and Molecular Biology Diagnostic Laboratory, Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP "Paolo Giaccone", Palermo, Italy (A.B.C., R.S., D.N., V.V., V.I., M.R.A.).
authors.forename: Antonina
authors.initials: A
authors.lastname: Ganci
authors.affiliation: From the Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy (A.B.C., R.S., D.N., V.I., A. Giammanco, M.D.P., A. Ganci, C.M.B., M.R.A.); and Molecular Biology Diagnostic Laboratory, Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP "Paolo Giaccone", Palermo, Italy (A.B.C., R.S., D.N., V.V., V.I., M.R.A.).
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Barbagallo
authors.affiliation: From the Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy (A.B.C., R.S., D.N., V.I., A. Giammanco, M.D.P., A. Ganci, C.M.B., M.R.A.); and Molecular Biology Diagnostic Laboratory, Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP "Paolo Giaccone", Palermo, Italy (A.B.C., R.S., D.N., V.V., V.I., M.R.A.). maurizio.averna@unipa.it abaldassare.cefalu@unipa.it.
authors.forename: Maurizio R
authors.initials: MR
authors.lastname: Averna
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D018389:Codon, Nonsense; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006579:Heterozygote; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D012720:Severity of Illness Index; D014280:Triglycerides / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C533813:CREB3L3 protein, human; D018389:Codon, Nonsense; D017362:Cyclic AMP Response Element-Binding Protein; D014280:Triglycerides
keywords: codon, nonsense; heterozygote; hypertriglyceridemia; mutation; triglycerides