The phenotypes of a hypercholesterolemia family with low density lipoprotein receptor exon 13 A606T mutation / 中华内科杂志

ObjectiveTo investigate the clinical phenotypes of familial hypercholesterolemia (FH) caused by exon 13 A606T mutation in low deusity lipoprotein receptor.MethodsClinical data of the suffered family were collected and analyzed,as well as measurement of perivascular intima-medial thickness and follow-mediated-dilation function by ultrasonography.ResultsThere were totally 11 sufferers including 4 males and 9 females,aged 8-90 years,with 2 homozygotes and 9 heterozygotes.Among them, one homozygote showed angina pectoris and hematuria,both homozygotes had skin xanthomata.TC,TG,LDL-C and HDL-C were(7.39 ± 1.30) mmol/L,(0.93 ± 0.36) mmol/L,( 11.76 ± 1.10) mmol/L and ( 1.22 ±0.17) mmol/L,respectively.The left/right sided intima-medial thickness of the common,internal,external and bulb carotid artery were ( 1.15 ±0.45) mm/( 1.30 ±0.60) mm,(0.82 ±0.30) mm/( 1.00 -0.66)mm,(0.77 ±0.28) mm/(0.78 ±0.30) mm and ( 1.40 ±0.59) mm/( 1.46 ±0.71 ) mm respectively.The brachial artery flow mediated dilation rate was (4.85 ±4.80)％.Echocardiography revealed 2 patients with cardiac valvular disease and 3 with atrium septum aneurysm. ConclusionFH patients show a variety of phenotypes incuding extraordinary hypercholesterolemia,subcutaneous xanthomata and premature coronary heart disease.

A genetic and clinical study in a family with familial hypercholesterolemia / 中华内科杂志

Objective To investigate the low density lipoprotein receptor (LDLR)gene and apolipoprotein (Apo) B gene mutation in a Chinese family with familial hypercholesterolemia(FH) and give the kindrids clinical check-ups. Methods After physical examination, the kindreds underwent ECG and ultrasound checks. Blood samples were tested for lipid profiles. The promoter and all eighteen exons of LDLR gene were investigated by using PCR and agarose gel electrophoresis in combination with DNA sequence analysis. The results were compared with the normal sequences in GenBank and FH database ( www. ucl. ac. uk/fh ) to find mutations. In addition, the apolipoprotein B100 gene for known mutations (R3500Q,R3531C,R3501W and R3480W)that cause familial defective ApoB100 (FDB)was also tested using the same method. Results A novel homozygous G ＞ A mutation at the 1581 bp of exon 10 was detected in the proband and his siblings. It caused a substitution of amimo acid Glu to Gly at codon 496. A novel heterozygous G ＞A mutation at the 1581 bp of exon 10 was detected in his parents. No mutations of R3500Q,R3531C,R3501W and R3480W of ApoB100 were observed. ECGs were normal. Atherosclerosis were found in all family members by ultrasound checks. Conclusions The homozygous G ＞ A mutation at the 1581 bp of exon 10 was first determined in our country. The change of amino acid Glu to Gly is responsible for FH of the family. The type of the gene mutation was not found in the FH database( www. ucl.ac. uk/ih). It's a new type of LDLR mutation.