title: [Identification of a novel splice mutation of low density lipoprotein receptor gene in a Chinese family with familial hypercholesterolemia].
abstract: OBJECTIVE
  To identify the mutation of low density lipoprotein receptor(LDLR) gene in a large Chinese family with familial hypercholesterolemia(F H) and make a discussion on the pathogenesis of FH at the molecular level.
  
  
  METHODS
  Investigations were made on a patient with the clinical phenotype of homozygous FH and his parents for mutations of promoter and all 18 exons of LDLR gene. Screening was carried out using Touch down PCR and a g arose gel electrophoresis, combined with DNA sequence analysis. The results were compared with the normal sequences in GenBank and FH database (www.ucl.uk/fh) t o find the mutation. Then the mutation was identified in other members of the family. In addition, the authors screened the apolipoprotein B(100) (apoB(100)) gene f or known mutations (R3500Q) that cause familial defective apoB(100) (FDB) by PCR-RFLP.
  
  
  RESULTS
  A novel homozygous IN III 5' GT --> AT mutation in the splice donor of LDLR intron 3 was detected in the homozygote propositus with FH. The mutation was also identified in four heterozygous carriers in his family. No mutations R3500Q of apoB(100)were observed.
  
  
  CONCLUSIONS
  A homozygous G --> A splice mutation in LDLR gene was first reported. The change of the splice donor in LDLR intron 3 may cause skipping of exon 3, which is responsible for FH. Perhaps it is a particular pathogenesis for Chinese people.
authors.affiliation: Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, PR China. linjie1998@sina.com.cn
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: Xiao-dong
authors.initials: XD
authors.lastname: Pan
authors.forename: Lan-ping
authors.initials: LP
authors.lastname: Du
authors.forename: Feng-ru
authors.initials: FR
authors.lastname: Shi
authors.forename: Yan-wen
authors.initials: YW
authors.lastname: Qin
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.forename: Heng-yi
authors.initials: HY
authors.lastname: Guo
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002681:China; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D008055:Lipids; D011973:Receptors, LDL; D004247:DNA