Homozygous deletion of exon 9 causes lipoprotein lipase deficiency: possible intron-Alu recombination.

P Benlian,J Etienne,J L De Gennes,L Noé,D Brault,A Raisonnier,F Arnault,J Hamelin,L Foubert,J C Chuat

doi:10.1016/s0022-2275(20)39913-2

Abstract

We studied a homozygous deletion in the lipoprotein lipase gene at the molecular level. Comprising the end of intron 8, the whole of exon 9, and about two-thirds of intron 9, this 2.136-kb deletion caused complete lipoprotein lipase deficiency and severe hypertriglyceridemia (type I hyperlipoproteinemia). Intron 9 of a normal control subject was also sequenced in order to define the exact borders of the deletion. Up to now, only the first 0.721 kb of intron 9 had been sequenced. Thus the complete sequence of intron 9 (3.090 kb) is now available. Three Alu sequences were characterized in the normal intron 9, while the proband had only the third complete Alu sequence. The first Alu sequence was located in the deleted region, and only the left arm of the second was present, as the deletion began near its center. A stem-loop structure involving a 14-nt region towards the end of intron 8 and an Alu sequence in intron 9 might have led to the deletion. Sequence analysis showed that the three Alu sequences belonged to the 40-million-year-old Alu-Sa subclass.

Highlights

We studied a homozygous deletion in the lipoprotein lipase gene at the molecular level
We report the molecular characterization of a novel defect [3] in the human Lipoprotein lipase (LPL) gene
We submitted the region between the middle of intron 8 and the beginning of exon 10 to polymerase chain reaction (PCR) amplification

Summary

Introduction

We studied a homozygous deletion in the lipoprotein lipase gene at the molecular level. Comprising the end of intron 8, the whole of exon 9, and about two-thirds of intron 9, this 2.136-kb deletion caused complete lipoprotein lipase deficiency and severe hypertriglyceridemia(type I hyperlipoproteinemia).Intron 9 of a normal control subject was sequenced in order to define the exact borders of the deletion. Only the first 0.721 kb of intron 9 had been sequenced. The complete sequence of intron 9 (3.090 kb) is available. Three Alu sequences were characterized in the normal intron 9, while the proband had only the third complete Alu sequence. A stem-loop structure involving a 14-nt region towards the end of intron 8 and an Alu sequence in intron 9 might have led to the deletion. Homozygous deletion of exon 9 causes lipoprotein lipase deficiency: possible intron-Alu recombination.

Methods

Results

Conclusion