ABSTRACT
Objective To evaluate the features of myocardial perfusion imaging (MPI) in patients with homozygous familial hypercholesterolemia (HoFH) and its influence factors.Methods Forty-two consecutive HoFH patients (21 males,21 females;average age:(14.8±8.4) years) were retrospectively enrolled in this study from June 2010 to November 2016.Diagnosis was proved by clinical and chromosome tests,and all patients underwent ATP stress and rest 99Tcm-methoxyisobutylisonitrile (MIBI) SPECT MPI with a two-day protocol.Summed stress score (SSS) and summed rest score (SRS) were acquired,and summed difference score (SDS;SSS-SRS) was calculated.Relations between SSS,SRS,SDS and age,lipid profile were analyzed.Two-sample t test,x2 test,multiple linear regression analysis and multivariate logistic regression were used to analyze the data.Results There were 24 patients with positive MPI results (SSS≥1),and females (76.2％,16/21) showed more positive MPI results than males (38.1％,8/21;x2=6.22,P＜0.05).Eighteen patients had negative MPI results.There were 6,8,10 patients with MPI positive results in ＜ 10 years group (n =14),10-18 years group (n =14) and ≥ 19 years group,respectively (x2=2.33,P＞0.05).Positive electrocardiograph (ECG) in ATP stress test was observed in 9 females (42.9％,9/21) and 3 males (14.3％,3/21;x2 =4.20,P＜0.05).Sixty-three (8.8％,63/714) abnormal myocardial perfusion segments (SSS≥ 1) were found,which was mainly (60.3％,38/63) distributed in myocardial regions supplied by left anterior descending branch (LAD).SSS was positively correlated with age and high density lipoprotein cholesterol (HDLC).SRS,SDS were positively correlated with HDLC and age respectively.Multivariate logistic regression analysis indicated that the female was the only independent risk factor to predict positive MPI (odds ratio=5.2,95％ CI:1.363-19.774).Conclusions In HoFH patients,abnormal myocardial perfusion had a rising trend with age increasing.Female patients are more likely to have abnormal MPI.Abnormal myocardial perfusion segments are mainly located in myocardial regions supplied by LAD.Age and gender are influence factors of abnormal MPI in HoFH patients.
ABSTRACT
Objective To determine LDLR gene mutation in 2 clinically diagnosed FH patients from Hubei province and provide basis for gene diagnosis of FH.Methods Clinical data of 2 FH patients and their parents were collected.The promoter region and exon 1 to exon 18 region of LDLR gene were amplified through PCR and the amplified products were analyzed by forward and reverse DNA sequencing.The mutations were identified after comparison with LDLR gene sequence in GenBank.The pathogenic gene mutations were confirmed according to both genotype and phenotype of FH probands.Results The levels of plasma TC of two probands were 12.79 and 11.98 mmol/L.respectively.No gene mutations were detected in region 3 500 to 3 531 of ApoB100. The mutations of LDLR gene were compound heterozygous mutations. The novel mutation 665G > T detected in the exon 4 of No. 1 proband's LDLR gene was heterozygous missense mutation. The novel mutation 1 358 +32C > T was detected in the exon 9 of No. 1 proband's LDLR gene.The mutations 665G > T ( paternal origin) and 1 358 + 32C > T ( maternal origin) were inherited from the parents. A novel mutation 1 257 C > A was detected in the exon 9 of No. 2 proband's LDLR gene, resulting the presence of a premature termination codon, which was different from 1 257 C > G reported in Belgium.Another heterozygous missense mutation 1 879 G > A was detected in exon 13. They were derived from paternal origin and maternal origin, respectively. Conclusions There are three novel gene mutations:665G >T, 1 358 +32C > T, 1 257C > A found in two probands with compound heterozygous mutations in LDLR respectively. They maybe play a potential role in FH pathogensis.