Analysis of low-density lipoprotein receptor gene mutations in a Chinese patient with clinically homozygous familial hypercholesterolemia.
OBJECTIVE
To screen the point mutation of the low-density lipoprotein receptor (LDL-R) gene in Chinese familial hypercholesterolemia (FH) patients, characterize the relationship between the genotype and the phenotype and discuss the molecular pathological mechanism of FH.


METHODS
A patient with clinical phenotype of homozygous FH and her parents were investigated for mutations in the promoter and all eighteen exons of the LDL-R gene. Screening was carried out using Touch-down PCR and direct DNA sequencing; multiple alignment analysis by DNASIS 2.5 was used to find base alteration, and the LDL-R gene mutation database was searched to identify the alteration. In addition, the apolipoprotein B gene (apo B) was screened for known mutations (R3500Q) that cause familial defective apo B100 (FDB) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).


RESULTS
Two new heterozygous mutations in exons 4 and 9 of the LDL-R gene were identified in the proband (C122Y and T383I) as well as her parents. Both of the mutations have not been published in the LDL-R gene mutation database. No mutation of apo B100 (R3500Q) was observed.


CONCLUSIONS
Two new mutations (C112Y and T383I) were found in the LDL-R gene, which may result in FH and may be particularly pathogenetic genotypes in Chinese people.
Laboratory of Infection and Immunity, Capital Institute of Pediatrics, Beijing 100020, China.
Shouchun
S
Cao
Lüya
L
Wang
Yanwen
Y
Qin
Jie
J
Lin
Bangjun
B
Wu
Shu
S
Liu
Xiaodong
X
Pan
Lanping
L
Du
Baosheng
B
Chen
D000328:Adult; D001055:Apolipoproteins B / Q000235:genetics; D044466:Asian People; D002648:Child; D002681:China; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics*
D001055:Apolipoproteins B; D011973:Receptors, LDL