[A compound heterozygote family of familial hypercholesterolemia due to new mutations].
OBJECTIVE
To investigate the molecular diagnosis method and possible molecular mechanism of the etiology of a hereditary genetic hypercholesterolemia family by scanning and analyzing the related genes of hereditary hypercholesterolemia in a clinically diagnosed proband and his family members.


METHODS
Molecular diagnosis was performed with PCR and then DNA sequencing of the promoter and 18 exons of low-density lipoprotein receptor (LDLR) gene and 3500 - 3531 fragment of apolipoprotein B-100 gene was carried out. The sequencing results were compared with the normal nucleotide sequence queried from the GeneBank database to discover the mutations.


RESULTS
Familial defective apolipoprotein B-100 was excluded, as no mutation was detected in the apolipoprotein B 3500 - 3531 fragment. Two new point mutations were detected in the exon 4 of the proband's LDLR gene, they were heterozygous 685delA (Del A at 685) and 386A > G. The sequencing in his parents and other family members showed that the two mutations were paternal origin (685delA) and maternal origin (386A > G) respectively and should be located in different alleles of the proband.


CONCLUSIONS
Molecular diagnosis in the family shows that the proband is a compound heterozygote and the newly detected LDLR gene mutations of 685delA and 386A > G are the possible molecular etiological basis of the disease in this family.
Chen
Kang
K
Department of Endocrinology, The Chinese PLA General Hospital, Beijing 100853, China.
Mu
Yi-ming
YM
Wang
Bao-an
BA
Guo
Qing-hua
QH
Lü
Zhao-hui
ZH
Dou
Jing-tao
JT
Lu
Ju-ming
JM
D017668:Age of Onset; D002648:Child; D004252:DNA Mutational Analysis; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011973:Receptors, LDL / Q000235:genetics*
D011973:Receptors, LDL