The Mutation Underlying Familial Hypercholesterolemia in a Taiwanese Family

Abstract

本研究係藉聚合酶連鎖反應及DNA定序，來檢視一位六歲的家族性高膽固醇血症(FH)患者，其低密度脂蛋白(LDL)受體基因的起動子及表現子序列，以了解其分子致因。結果發現患者的LDL受體的配體結合部位上發生E207K突變，即第207個胺基酸由麩胺酸(Glu)轉變為離胺酸(Lys)。進一步的MnlI限制酵素切割檢測顯示，患者的E207K突變係遺傳至祖母，其妹妹弟弟亦帶有此突變。LDL受體基因突變的確認可明確的定義患者的高血脂原因，以利早期安排適當的治療、進行出生前診斷、家族分析等。

DNA screening for low-density lipoprotein (LDL) receptor mutations was performed in a clinically diagnosed six-year-old familial hypercholesterolemia (FH) patient. The promoter region and the coding sequence of the LDL receptor gene were amplified by means of polymerase chain reaction and subjected to DNA sequencing to study the molecular lesion. A G→A transition in codon 207, changing Glu207 to Lys (E207K) in the ligand-binding domain of the LDL receptor, was identified. Analysis with MnlI endonuclease digestion showed this mutation to be inherited from paternal grandmother. The proband's two siblings also carried the mutation. Identification of the disease-causing mutation can clearly define the cause of patient's hyperlipidemia and allow appropriate early treatment and antenatal and family studies.