Catalytic triad residue mutation (Asp super(156) arrow right Gly) causing familial lipoprotein lipase deficiency. Co-inheritance with a nonsense mutation (Ser super(447) arrow right Ter) in a Turkish family

• Published in: The Journal of biological chemistry Vol. 266; no. 22; pp. 14418 - 14424
• Main Authors: Faustinellar, F, Chang, A, van Biervliet, JP, Rosseneu, M, Vinaimont, N, Smith, L C, Chen, San-Hwan, Chan, L
• Format: Journal Article
• Language: English
• Published: 01-01-1991
• Subjects: genes; hereditary diseases; hyperlipoproteinemia; inborn errors of metabolism; polymerase chain reaction
• ISSN: 0021-9258

We studied the molecular basis of familial Type I hyperlipoproteinemia in two brothers of Turkish descent who had normal plasma apolipoprotein C-II levels and undetectable plasma post-heparin lipoprotein lipase (LPL) activity. We cloned the cDNAs of LPL mRNA from adipose tissue biopsies obtained from these individuals by the polymerase chain reaction and directional cloning into M13 vectors. Direct sequencing of pools of > 2000 cDNA clones indicates that their LPL mRNA contains two mutations: a missense mutation changing codon 156 from GAU to GUU predicting an ASP super(156) arrow right Gly substitution and a nonsense mutation changing the codon for Ser super(447) from UCA to UGA, a stop codon, predicting a truncated LPL protein that contains 446 instead of 448 amino acid resides. Both patients were homozygous for both mutations.