A novel mutation (Cys308Phe) of the LDL receptor gene in families from the South-Eastern part of Poland

作者：Walus Miarka Malgorzata^*; Sanak Marek; Idzior Walus Barbara; Miarka Przemyslaw; Witek Przemyslaw; Malecki Maciej T; Czarnecka Danuta

来源：Molecular Biology Reports, 2012, 39(5): 5181-5186.

DOI：10.1007/s11033-011-1314-0

• Familial hypercholesterolemia
• LDL-receptor
• Atherosclerosis
• Missense mutation
• Xanthoma

The purpose of this investigation was to characterize a new mutation in the LDL-receptor (LDLR) gene in three families with clinically diagnosed familial hypercholesterolemia (FH) from the South-Eastern part of Poland. Mutational screening with exon by exon sequencing analysis was performed in all probands. The novel mutation c986G %26gt; T (Cys308Phe) in the exon 7 of LDLR gene was found in three apparently unrelated probands with FH. Analysis of the receptor activity of peripheral blood lymphocytes by binding and uptake of DiL-LDL showed a significant reduction (by 24% versus healthy control) of the fluorescent label in the lymphocytes of patients heterozygous for this mutation. Concentrations of serum LDL-C in probands before treatment were between 9.5 and 10.5 mmol/l. All patients had corneal arcus and tendon xanthoma. Clinically, families were characterized by premature coronary artery disease. This mutation occurred relatively frequently in our group of patients with FH, but this could be explained by a founder effect since we demonstrated their common ancestors.

• 出版日期2012-5