Detection of familial defective apoB (FDB) mutations in hypercholesterolemic children and adolescents by denaturing high performance liquid chromatography (DHPLC)

作者：Nelken Joanna; Meshkani Reza; Chahal Nita; McCrindle Brian; Adeli Khosrow^*

来源：Clinical Biochemistry, 2008, 41(6): 395-399.

DOI：10.1016/j.clinbiochem.2007.12.018

• familial defective apoB
• hypercholesterolemia
• mutation
• apolipoprotein B
• denaturing HPLC

Objective: To seek apolipoprotein B (apoB) gene mutations in children and adolescents presenting to a lipid clinic with hypercholesterolemia and suspected of familial defective apoB (FDB), employing a new automated denaturing high performance liquid chromatography (DHPLC) method.
Design and methods: 131 patients between the ages of 3 and 18 years were screened for the presence of FDB mutations using DHPLC. Patients who exhibited aberrant DHPLC chromatograms were sequenced.
Results: Three patients were found to be positive for the R3500Q mutation in which a single nucleoticle G -> A transition resulted in arginine to glutamine substitution at codon 3500 in exon 26 of the apoB-100 gene. All three subjects had elevated total cholesterol and LDL cholesterol levels, and high or borderline high plasma apoB levels. No R350OW or R3531C apoB mutations were found.
Conclusions: Automated DHPLC can be readily applied in rapid screening of hypercholesterolemic children presenting to a lipid clinic. Using DHPLC, this study revealed that the FD13 mutation (R3500Q) is an important contributing factor to hypercholesterolemia observed in a pediatric lipid clinic population.

• 出版日期2008-4