Mutation analysis and prenatal diagnosis for 50 pedigrees affected with Duchenne/Becker muscular dystrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish individualized prenatal diagnosis program for families affected with Duchenne/Becker muscular dystrophy (DMD/BMD) and different clinical background using a variety of methods.</p><p><b>METHODS</b>Multiplex ligation-dependent probe amplification (MLPA) was performed on 50 patients suspected for DMD/BMD. For single exon deletions of the DMD gene, PCR was used for validating the results. For those without any deletion or duplication, Sanger sequencing was used to screen for DMD gene mutations in the children and their mothers. Prenatal genetic testing was provided to female carriers using chorionic villus, amniocentesis or cord blood samples. To ensure the accuracy of diagnosis, all prenatal specimens were also subjected to linkage analysis.</p><p><b>RESULTS</b>Among the 50 patients with DMD/BMD, 23 harbored large deletions, 11 only had single exon deletions, 10 harbored duplications, and 5 had small scare mutations. No mutation was detected in one family. For 37 women undergoing prenatal diagnosis, 10 fetuses were identified as affected males, 6 were female carriers, while 21 were not found to carry any mutation. Testing of creatine kinase was consistent with the results of prenatal diagnosis. For a patient harboring exon 51 deletion, the same mutation was found in a fetus but not in their mother. The proband and fetus had inherited the same haplotype, which suggested that the mother probably has germline mosaicism for the mutation.</p><p><b>CONCLUSION</b>Application of individualized methods for analyzing pregnant women with different clinical background can minimize the risk for giving birth to further children affected with DMD/BMD.</p>

Association of EPHX2 rs 751141 polymorphisms with coronary heart disease / 实用医学杂志

Objective To study the correlation between EPHX2 gene rs751141 polymorphisms and coronary heart disease (CHD) in Chinese population.Methods Totally 108 patients having more than one major coronary vessel with at least 50％ stenosis defined by Coronary angiography were selected as CHD group and control group consisted of 112 healthy subjects.Rs751141 polymorphisms were detected by PCR and gene sequence.Results Three kinds of genotypes at the rs751141 were detected,and no deviation was observed from HardyWeinberg equilibrium.There was statistical difference between the two groups regarding the distribution of the genotype frequencies and the frequency of allele C (P ＜ 0.05).Conclusion It suggests that rs751141 polymorphism is associated with CHD in Chinese population and the C allele might be a risk factor of CHD.

Analysis and prenatal diagnosis of deafness-related gene mutations in patients with nonsyndromic hearing loss / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze deaf-related genes in patients with nonsyndromic hearing loss (NSHL) and set up a prenatal diagnosis system for such patients.</p><p><b>METHODS</b>Nine NSHL families were collected. Potential mutations of GJB2 (35delG, 176del16, 235delC, 299delAT), SLC26A4 (2168A> G, IVS7-2A> G), GJB3 (538C> T) and mtDNA (1494C> T, 12S rRNA 1555A> G) were detected by direct sequencing. Maternal blood contamination was excluded prior to the testing.</p><p><b>RESULTS</b>Sixteen patients from 4 families were detected with GJB2 mutations, 8 patients from 2 families were found with SLC26A4 mutations, and 4 patients from 2 families were found with mutations in mtDNA. For 2 patients from one remaining family, no mutations were found with above genes.</p><p><b>CONCLUSION</b>A diagnostic system for NSHL has been established, which may provide a basis for prenatal diagnosis and genetic counseling to NSHL families.</p>

Establishment of median for the antepartum screening biomarkers in normal pregnant women / 中华检验医学杂志

Objective To evaluate the differences of α-fetoprotein (AFP), ffeeβ-human chorionic gnnadotropin (HCG) indexes in 3 foreign median databases for antepartum risk screening, and establish the median databases of normal pregnant women in Wenzhou for antepartum screening of AFP, free-β-HCG indexes through the suitable median computational models. Methods The levels of AFP and free β-HCG of 20054 normal pregnant women in Wenzhou were detected by time-resolved fluorometry. The data in this paper were compared with the data of 2T-risk ( 2T), Lifecycle-2. 2 (LC2.2 ) and Lifecycle -3.0 (LC3.0) by double-factor ANOVA. The differences between the data in the paper and the data from Shenyang and Ningbo were analyzed. The median database of Wenzhou pregnant women was established by the suitable regression model, with the stability of nonlinear regression models of the 3 software assessed by model correcting fitting, distribution mean of model fitting logarithmic and standard deviation. Results The levels of AFP and freeβ- hCG reported here were 10% and 16% higher than the data of 2T-risk, 15% and 20% higher than that of LC 2. 2, 6% and 17% higher than that of LC 3.0 respectively. The differences were statistically significant. ( FAFP = 161. 757 ,P < 0. 01 ; Ffree-β-HCG = 58. 261, P < 0.01 ). The levels of AFP and free β- hCG in Wenzhou were 2% higher and 3% lower than that of Shenyang, 1% and 2% higher than that of Ningbo. There was no statistical difference of AFP levels among Wenzhou , Shenyang and Ningbo( FAFP = 0. 174 ,P =0. 840) while the differences of free-β-hCG were statistically significant( F<,free-β-HCG> = 13.303 ,P < 0. 01 ). The differences of quadratic equation regression model, exponent quadratic function regression model and exponent quadru-function regression model of 2T, LC-2. 2 and LC-3.0 were not remarkable. The exponent quadru-function regression model was the best. Conclusions There are significant differences between the data from Wenzhou, Shenyang and Ningbo and the data of T-2 risk, LC-2. 2, LC -3.0. The discrepancy is due to the ethnic and different parameters of regression models. So the model parameters and the median databases are urgently required in China. The differences of large sample size of AFP from Wenzhow, Shengyang and Ningbo are not significant, while the differences of free-β- hCG from Wenzhow, Shengyang and Ningbo is remained because of its instability. The levels from Wenzhow and Ningbo are near. It is suggested that the laboratories with small sample size can establish their own laboratory parameters using the reference obtained from large sample size under the same experimental conditions. There are no significant differences of stability among regression computational models in the 3 software. The exponent quadru-function regression model can be used to establish the median databases for the screening with the similar data distribution in the paper.