title: Identification of LDLR mutations in two Chinese pedigrees with familial hypercholesterolemia.
abstract: Familial hypercholesterolemia (FH) is an autosomal dominant, inherited disease (OMIM 143890) characterized by elevated serum cholesterol bound to low-density lipoprotein (LDL). It is mainly caused by mutations of the low-density lipoprotein receptor gene (LDLR). In this study, we investigated two Chinese pedigrees with FH. The probands were a 9-year-old boy and a 1-year-old boy, who had high LDL-C levels. The proband in family A showed skin xanthoma. We sequenced the promoter and all exons and exon-intron boundaries of the LDLR gene to detect potential mutations. Compound heterozygote of c.1747C>T and c.2054C>T was detected in the proband of family A, and a heterozygous indel mutation c.551_553 delGTAinsTT was discovered in the second family. The c.1747C>T and c.2054C>T mutations, which have been reported previously, result in His583Tyr and Pro685Leu substitutions, respectively. The novel c.551_553 delGTAinsTT indel mutation causes a frameshift, which results in a p.Cys184Phe fs21X mutation in the corresponding protein.
authors.affiliation: Research Division of Birth Defects, Institute of Pediatric Translational Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China
authors.forename: Ru-En
authors.initials: RE
authors.lastname: Yao
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Geng
authors.forename: Zhaojing
authors.initials: Z
authors.lastname: Zheng
authors.forename: Tingting
authors.initials: T
authors.lastname: Yu
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Yu
authors.forename: Qihua
authors.initials: Q
authors.lastname: Fu
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005190:Family; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000208:ethnology / Q000235:genetics*; D007223:Infant; D008297:Male; D020125:Mutation, Missense / Q000502:physiology; D010375:Pedigree; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: C573412:LDLR protein, human; D011973:Receptors, LDL