We report a large family in which four members showed a plasma lipid profile consistent with the clinical diagnosis of familial combined hyperlipidemia (FCHL). One of these patients was found to have markedly reduced HDL cholesterol (HDL-C) (0.72 mmol/l) and Apo A-I (72 mg/dl) levels, a condition suggestive of the presence of a mutation in one of the HDL-related genes. The analysis of APOA1 gene revealed that this patient was heterozygous for a cytosine insertion in exon 3 (c.49–50 ins C), resulting in a frame-shift and premature stop codon at position 26 of pro-Apo A-I (Q17PFsX10). This novel mutation, which prevents the synthesis of Apo A-I, was also found in four family members, including three siblings and the daughter of the proband. Carriers of Apo A-I mutation had significantly lower HDL-C and Apo A-I than non-carriers family members (0.77 ± 0.15 mmol/l vs. 1.15 ± 0.20 mmol/l, P < 0.005; 71.4 ± 9.1 mg/dl vs. 134.0 ± 14.7 mg/dl, P < 0.005, respectively). Two of the APOA1 mutation carriers, who were also heavy smokers, had fibrous plaques in the carotid arteries causing mild stenosis (20%). The intimal-media thickness in the two other adult carriers was within the normal range. The other non-carriers family members with FCHL had either overt vascular disease or carotid atherosclerosis at ultrasound examination. This observation suggests that the low HDL-C/low Apo A-I phenotype may result from a genetic defect directly affecting HDL metabolism, even in the context of a dyslipidemia which, like FCHL, is associated with low plasma HDL-C.

A novel mutation of the apolipoprotein A-I gene in a family with familial combined hyperlipidemia / Pisciotta, L; Fasano, Tommaso; Calabresi, L; Bellocchio, A; Fresa, R; Borrini, C; CALANDRA BUONAURA, Sebastiano; Bertolini, S.. - In: ATHEROSCLEROSIS. - ISSN 0021-9150. - STAMPA. - 198:1(2008), pp. 145-151. [10.1016/j.atherosclerosis.2007.09.017]

A novel mutation of the apolipoprotein A-I gene in a family with familial combined hyperlipidemia

FASANO, Tommaso;CALANDRA BUONAURA, Sebastiano;
2008-01-01

Abstract

We report a large family in which four members showed a plasma lipid profile consistent with the clinical diagnosis of familial combined hyperlipidemia (FCHL). One of these patients was found to have markedly reduced HDL cholesterol (HDL-C) (0.72 mmol/l) and Apo A-I (72 mg/dl) levels, a condition suggestive of the presence of a mutation in one of the HDL-related genes. The analysis of APOA1 gene revealed that this patient was heterozygous for a cytosine insertion in exon 3 (c.49–50 ins C), resulting in a frame-shift and premature stop codon at position 26 of pro-Apo A-I (Q17PFsX10). This novel mutation, which prevents the synthesis of Apo A-I, was also found in four family members, including three siblings and the daughter of the proband. Carriers of Apo A-I mutation had significantly lower HDL-C and Apo A-I than non-carriers family members (0.77 ± 0.15 mmol/l vs. 1.15 ± 0.20 mmol/l, P < 0.005; 71.4 ± 9.1 mg/dl vs. 134.0 ± 14.7 mg/dl, P < 0.005, respectively). Two of the APOA1 mutation carriers, who were also heavy smokers, had fibrous plaques in the carotid arteries causing mild stenosis (20%). The intimal-media thickness in the two other adult carriers was within the normal range. The other non-carriers family members with FCHL had either overt vascular disease or carotid atherosclerosis at ultrasound examination. This observation suggests that the low HDL-C/low Apo A-I phenotype may result from a genetic defect directly affecting HDL metabolism, even in the context of a dyslipidemia which, like FCHL, is associated with low plasma HDL-C.
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A novel mutation of the apolipoprotein A-I gene in a family with familial combined hyperlipidemia / Pisciotta, L; Fasano, Tommaso; Calabresi, L; Bellocchio, A; Fresa, R; Borrini, C; CALANDRA BUONAURA, Sebastiano; Bertolini, S.. - In: ATHEROSCLEROSIS. - ISSN 0021-9150. - STAMPA. - 198:1(2008), pp. 145-151. [10.1016/j.atherosclerosis.2007.09.017]
Pisciotta, L; Fasano, Tommaso; Calabresi, L; Bellocchio, A; Fresa, R; Borrini, C; CALANDRA BUONAURA, Sebastiano; Bertolini, S.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/636878
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