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

Abstract 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 .