title: Two novel mutations of the LDL receptor gene associated with familial hypercholesterolemia in a Chinese family.
abstract: BACKGROUND
  Familial hypercholesterolemia (FH) is a type of dominant autosomal disease that causes high levels of plasma low-density lipoprotein cholesterol (LDL-C). In the past years, molecular data related to FH were limited in China. Now, to gain more information about FH, we analyzed one proband with a severe FH phenotype as well as his relatives.
  
  
  METHODS
  After the entire coding sequence and the intron-exon junctions of the low-density lipoprotein receptor (LDLR) gene were amplified using PCR, we sequenced the LDLR gene of a Chinese FH family. RT-PCR was used to detect changes in the mRNA.
  
  
  RESULTS
  Two novel mutations were identified in the LDLR gene of this family. One, W165X, was a G > A substitution at the third nucleotide of codon 165. The other, IVS5-1G > A, was also a G > A substitution at the acceptor splice site of intron 5. The most striking discovery is that the proband was heterozygous for W165X but homozygous for IVS5-1G > A. The cDNA sequencing showed that the IVS5-1G > A mutation caused the insertion of 10 nucleotides, namely GCTCTCACAA, between exon 5 and exon 6.
  
  
  CONCLUSIONS
  The two nucleotide variations are thought to be the FH-causing mutations because the co-segregation of the mutant allele with the phenotype of FH has been shown in this Chinese family. These data show an increase in the mutational spectrum of FH in China and verify a scarce mutational form in the LDLR gene.
authors.affiliation: Department of Cardiothoracic Surgery, Second Xiangya Hospital of Central South University, Changsha 410011, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Qi-hua
authors.initials: QH
authors.lastname: Gong
authors.forename: Zhi-guo
authors.initials: ZG
authors.lastname: Xie
authors.forename: Zong-min
authors.initials: ZM
authors.lastname: Liang
authors.forename: Zheng-mao
authors.initials: ZM
authors.lastname: Hu
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Jia-hui
authors.initials: JH
authors.lastname: Xia
authors.forename: Yi-feng
authors.initials: YF
authors.lastname: Yang
mesh_terms: D000328:Adult; D002648:Child; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D011973:Receptors, LDL