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Background Familial hypercholesterolemia (FH) is a type of dominant autosomal disease that causes high levels ofplasma 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 detectchanges in the mRNA.Results Two novel mutations were identified in the LDLR gene of this family.One,W165X,was a G>A substitution atthe third nucleotide of codon 165.The other,IVS5-1G>A,was also a G>A substitution at the acceptor splice site of intron5.The most striking discovery is that the proband was heterozygous for W165X but homozygous for IVS5-1G>A.ThecDNA 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 ofthe mutant allele with the phenotype of FH has been shown in this Chinese family.These data show an increase in themutational spectrum of FH in China and verify a scarce mutational form in the LDLR gene.Chin Med J 2007;120(19):1694-1699
Background Familial hypercholesterolemia (FH) is a type of dominant autosomal disease that causes high levels of plasma low-density lipoprotein cholesterol (LDL-C) .In 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 atthe third nucleotide of codon 165. other, IVS5-1G> A, also also a G> A substitution at the acceptor splice site of intron 5. 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-amplifying 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 themutational spectrum of FH in China and verify a scarce mutational form in the LDLR gene. Chin Med J 2007; 120 (19): 1694-1699