Apolipoprotein C-II Tuzla: a novel large deletion in APOC2 caused by Alu-Alu homologous recombination in an infant with apolipoprotein C-II deficiency.

Backgrounds: Familial apolipoprotein (apo) C-II deficiency is a very rare inherited disorder characterized by chylomicronemia. Since the discovery in 1978, reports on apo C-II deficient patients have been limited and only 13 different mutations in APOC2, a gene encoding apo C-II protein, were identified.

Objectives: The objective is to investigate the biochemical and genetic features of a 3-month-old Bosniak girl with chylomicronemia whose apo C-II protein was undetectable in her plasma.

Methods: APOC2, LPL, APOA5, and GPIHBP1 were sequenced. Isoelectrofocusing and immunoblotting of chylomicrons and VLDL fraction from the patient were performed.

Results: Sequence analysis demonstrated a large deletion of 2978 base pairs in APOC2, which encompassed exons 2, 3, and 4. The patient was homozygous for the deletion. The 5' part of the breakpoint was located in an Alu Sx repetitive element in intron 1 of APOC2, whereas the 3' part of the breakpoint was in another Alu Sx between APOC2 and CLPTM1, a gene flanking APOC2. We speculate that the deletion was caused by a homologous recombination between two Alu Sx elements. No mutations were detected in LPL, APOA5, and GPIHBP1. Isoelectrofocusing and immunoblotting confirmed the absence of apo C-II protein.

Conclusions: We diagnosed the patient as having apo C-II deficiency and designated the novel large deletion as apo C-II Tuzla. This is the first description of apo C-II deficiency caused by Alu-Alu recombination in APOC2.