Pseudodominance of lipoprotein lipase (LPL) deficiency due to a nonsense mutation (Tyr302 > Term) in exon 6 of LPL gene in an Italian family from Sardinia (LPLOlbia)

被引:14
作者
Bertolini, S
Simone, ML
Pes, GM
Ghisellini, M
Rolleri, M
Bellocchio, A
Elicio, N
Masturzo, P
Calandra, S
机构
[1] Univ Genoa, Dept Internal Med, Unit Vascular Dis Prevent, I-16126 Genoa, Italy
[2] Univ Sassari, Inst Clin Biochem, I-07100 Sassari, Italy
[3] Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy
关键词
genetic screening; lipoprotein lipase deficiency; nonsense mutation; primary hyperchylomicronemia;
D O I
10.1034/j.1399-0004.2000.570209.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We analyzed the molecular defect in the lipoprotein lipase (LPL) gene of a young boy from Sardinia who had primary hyperchylomicronemia, pancreatitis, and a complete LPL deficiency in post-heparin plasma. Analysis of LPL gene was performed by using single strand conformation polymorphism (SSCP) and direct sequencing of SSCP-positive region. The proband was homozygous for a C > A transversion in exon 6, which converts the codon for tyrosine at position 302 into a termination codon and eliminates an RsaI restriction site; this allowed the rapid screening of the proband's family members, among whom nine heterozygotes and one additional homozygote were identified. The homozygote was the proband's paternal grandmother who had shown the first clinical manifestation (recurrent pancreatitis) of LPL deficiency at the age of 54 years. LPL mutation carriers showed a mild dyslipidemic phenotype characterized by a reduction of high density lipoprotein-cholesterol (HDL-C) levels, HDL-C/total cholesterol ratio, and low density lipoprotein (LDL) size, associated with a variable increase of triglyceride levels. Five of these carriers were also heterozygotes for beta degrees-thalassemia (Q39X mutation). In these double mutation carriers, plasma HDL-C levels were higher and plasma triglycerides tended to be lower than in carriers of LPL mutation alone. The Tyr(302) > Term mutation encodes a truncated protein of 301 amino acids that is probably not secreted by the LPL producing cells. This is the first mutation of LPL gene found in Sardinians.
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页码:140 / 147
页数:8
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