A major insertion accounts for a significant proportion of mutations underlying human lipoprotein lipase deficiency.

Abstract

Lipoprotein lipase (LPL; triacylglyceroprotein acylhydrolase, EC 3.1.1.34) is an important enzyme involved in triacylglycerol metabolism. Primary LPL deficiency is a genetic disorder that is usually manifested by a severe elevation in triacylglycerol levels. We have used a recently isolated LPL cDNA clone to study 15 probands from 11 families with this inherited disorder. Surprisingly, 7 of the probands from 4 families, of different ancestries, had a similar insertion in their LPL gene. In contrast to other human genetic disorders, where insertions are rare causes of mutation, this insertion accounts for a significant proportion of the alleles causing LPL deficiency. Detailed restriction mapping of the insertion revealed that it was unlikely to be a duplication-of neighboring DNA and that it was not similar to the consensus sequence of human Li repetitive elements. This suggests that there must be other mechanisms of insertional mutagenesis in human genetic disease besides transposition of mobile Li repetitive elements.

Familial chylomicronemia (type I hyperlipoproteinemia) due to a single missense mutation in the lipoprotein lipase gene.

“…First, transmission of LPL mutations in families can be traced using restriction fragment length polymorphisms (RFLP). Recent studies utilizing this technique identified gross alterations in the LPL gene responsible for primary LPL deficiency in a significant number of type I hyperlipoproteinemias (31,32). An alternative and more sensitive approach, based on DNA sequence analysis, involves the direct identification of the deficiency-causing mutation in the LPL gene.…”

La deficience en lipoproteine lipase chez les canadiens francais

“…Le syndrome clinique de la déficience primaire en lipoprotéine lipase peut être décelé tôt dans l'enfance et se présente d'abord avec des douleurs abdominales (Langlois et al 1989); c'est d'ailleurs le symptôme le plus commun (75% des cas) (Rane et al 1984] (Guyot et al 1986). La douleur abdominale est habituellement localisée au milieu de l'épigastre et irradie dans le dos.…”

“…De plus, les patients présentent un plasma lactescent (Langlois et al 1989) ). Des pertes de mémoire et de la dépression ont aussi été rapportées chez certains patients ayant une hyperchylomicronémie .…”

“…Enfin, la sévérité des symptômes est proportionnelle à la concentration plasmatique en chylomicrons (Agarwal et al 1985) 1.1.4 Physiologie Les symptômes cliniques de la déficience en LPL familiale sont la conséquence d'une accumulation des chylomicrons dans le sang due à la déficience en lipoprotéine lipase (Kern et al 1990). La lipoprotéine lipase (LPL; triaglycero-protéine acylhydrolase, EC 3.1.134) qui est une glycoprotéine constituée de 448 acides aminés est synthétisée par de nombreux tissus parenchymateux, incluant les tissus adipeux, musculaires et cardiaques (Auwerx et al1989;Bergeron et al1991a;Langlois et al 1989; (Bergeron et al 1991a;). …”

The LPL gene in individuals with familial combined hyperlipidemia and decreased LPL activity.

“…PCR products for exons 4, 5, and 6 were made for each subject, purified by electrophoresis in low-melting-point agarose (Seaplaque), 26 and sequenced by the chain-termination method using 35 S-dATP. 27 Restriction digests with £coRI and Stu I with 5 /xg genomic DNA were run in 1% agarose gels, and Southern analysis was performed as described in Langlois et al 28 Results SSCP analysis of exons 1 through 9 and exon-intron junctions identified sequence variants in exons 2, 3, and 9. No variants were found in exons 1,4, 5, 6, 7, or 8.…”