Recurrent mutations of the apolipoprotein A-I gene in three kindreds with severe HDL deficiency

摘要: Two siblings with high density lipoprotein (HDL) deficiency and no plasma apolipoprotein A-I (Apo A-I) were found to be homozygous for a cytosine deletion in exon 3 of Apo gene (c.85 del C, Q5FsX11). This mutation causes frameshift leading premature stop codon abolishes the synthesis A-I. Although both had corneal opacifications planar xanthomas, only one them coronary artery disease, probably as result mildly elevated LDL levels. In two other unrelated subjects HDL was due heterozygosity nucleotide substitution 4 (c.494 T>G, L141R). Both mutations reported previously an Italian kindred which included compound heterozygotes simple heterozygotes. We investigated all carriers these three kindreds reported. Plasma HDL-C levels lower than non-carrier family members. These levels, however, L141R c.85 C. Haplotype analysis performed using several polymorphisms suggested that C are likely recurrent mutations.