title: Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C-->T mutation of low-density lipoprotein receptor gene.
abstract: BACKGROUND
  Familial hypercholesterolemia (FH), caused by low density lipoprotein (LDL) receptor (LDL-R) gene mutations, is associated with increased risk of premature coronary heart disease. Until now, limited molecular data concerning FH are available in China. The present study described the clinical profiles and cell biological defects of a Chinese FH kindred with novel LDL-R gene mutation.
  
  
  METHODS
  The patient's LDL-R gene coding region was sequenced. The patient's lymphocytes were isolated and the LDL-R expression, binding and up-take functions were observed by immunohistochemistry staining and flow cytometry detection. The patient's heart and the major large vessels were detected by vessel ultrasound examination and myocardial perfusion imaging (MPI).
  
  
  RESULTS
  The patient's LDL-R expression, LDL binding and up-take functions were significantly lower than normal control (39%, 63% and 76% respectively). A novel homozygous 1439 C-->T mutation of the LDL-R gene was detected in the patient and his family. ECG showed atypical angina pectoris. Echocardiogram showed stenosis of the coronary artery and calcification of the aortic valve and its root. Blood vessel ultrasound examination showed the thickness of large vessel intima, and the vessel lumen was narrowed by 71%. MPI showed ischemic changes.
  
  
  CONCLUSIONS
  The LDL-R synthesis dysfunction of FH patients leads to arterial stenosis and calcification, which are the major phenotype of the clinical disorder. The mutation of the LDL-R gene is determined. These data increase the mutational spectrum of FH in China.
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Lu-ya
authors.initials: LY
authors.lastname: Wang
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.forename: Jun-hui
authors.initials: JH
authors.lastname: Xia
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yong
authors.forename: Lan-ping
authors.initials: LP
authors.lastname: Du
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Pan
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
authors.forename: Bao-sheng
authors.initials: BS
authors.lastname: Chen
authors.forename: Zhi-sheng
authors.initials: ZS
authors.lastname: Jiang
mesh_terms: D000328:Adult; D002675:Child, Preschool; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics* / Q000502:physiology*
chemical_list: D011973:Receptors, LDL