title: A nonsense mutation in the apolipoprotein C-IIPadova gene in a patient with apolipoprotein C-II deficiency.
abstract: The apo C-II gene from a patient with apo C-II deficiency has been sequenced after amplification by the polymerase chain reaction. A substitution of an adenosine for a guanosine at position 3002 in exon 3 of the patient's gene was identified by sequence analysis. This mutation leads to the introduction of a premature termination codon (TAA) at a position corresponding to amino acid 37 of mature apo C-II and to the formation of a new Rsa I restriction enzyme site not present in the normal apo C-II gene. Amplification of DNA from family members by the polymerase chain reaction and digestion with Rsa I established that the patient is a true homozygote for the mutation. Analysis of the patient's plasma by two-dimensional gel electrophoresis and immunoblotting detected an apo C-II that exhibited abnormal electrophoretic mobility. We propose that the C to A substitution in the apo C-IIPadova gene is the primary genetic defect that leads to premature termination and the synthesis of a truncated 36 amino acid apo C-II that is unable to activate lipoprotein lipase.
authors: Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
authors: S S
authors: SS
authors: Fojo
authors: P
authors: P
authors: Lohse
authors: C
authors: C
authors: Parrott
authors: G
authors: G
authors: Baggio
authors: C
authors: C
authors: Gabelli
authors: F
authors: F
authors: Thomas
authors: J
authors: J
authors: Hoffman
authors: H B
authors: HB
authors: Brewer
mesh_terms: D000241:Adenosine / Q000235:genetics; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000235:genetics; D015152:Blotting, Northern; D015139:Blotting, Southern; D003062:Codon; D003596:Cytosine; D004247:DNA / Q000032:analysis / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis
chemical_list: D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D003062:Codon; D012313:RNA; D003596:Cytosine; D004247:DNA; D000241:Adenosine