Genetic analysis of a case with mosaicism of a small supernumerary marker chromosome derived from idic(15) / 中华医学遗传学杂志

OBJECTIVE@#To determine the origin of a mosaicism small supernumerary marker chromosome (sSMC) by cytogenetic and molecular analysis.@*METHODS@#Karyotype analysis, fluorescence in situ hybridization (FISH) and SNP-array were carried out.@*RESULTS@#The karyotype of the patient was mos47,XX,+mar[45]/48,XX,+2mar[3]/46,XX[52]; the SNP-array result was arr[hg19]15q11.1q11.2 (20 161 372-24 314 675)×3, and the repeat fragment was about 4.15 Mb. FISH showed that approximately 50% of the cells have contained a sSMC with double D15Z1 probe site segments derived from abnormal idic(15). This sSMC did not contain SNRPN and PML probe fragments of Prader-Willi syndrome/Angelman syndrome.@*CONCLUSION@#When the patient's karyotype and phenotype are inconsistent, cytogenetic and molecular biology technologies should be combined to clarify the karyotype and gene location, so as to provide more accurate genetic consultation for the follow-up treatments.

Genetic analysis of an individual with a fragile site at 16q22 / 中华医学遗传学杂志

OBJECTIVE@#To analyze a patient with infertility and a fragile site found at 16q22 by using cytogenetic methods.@*METHODS@#Peripheral blood sample was taken from the patient and subjected to chromosomal karyotyping and single nucleotide polymorphism microarray (SNP-array) analysis.@*RESULTS@#The patient was found to be a mosaicism for a fragile site at 16q22, which has a variable morphology and cannot be induced by folic acid treatment. No abnormality was found by SNP-array analysis.@*CONCLUSION@#A rare fragile site, which can be induced without folic acid treatment, has been identified at 16q22. The strategy of assisted reproduction for such individuals is yet to be explored.

Arachidonic acid metabolic pathway-related genes interactions increase the incidences of stroke and vulnerable plaques / 中华神经科杂志

Objective To investigate whether metabolic pathway-related gene polymorphisms are associated with arterial plaque stability and their gene-gene interactions increase the risk of cerebral infarctions.Methods Totally 294 patients with atherothrombosis stroke admitted to the Department of Neurology, the Third Affiliated Hospital of Wenzhou Medical University from September 2010 to December 2012 were divided into a carotid vulnerable plaque group ( n=69 ) and a stable plaque group ( n=225 ) according to the results of carotid B-mode ultrasonography.A total of 282 healthy volunteers excluded carotid plaque and stroke were enrolled as well.Genetic polymorphisms of ALOX5AP and CYP3A5, CYP2C9*2, CYP2C9*3 and EPHX2 were genotyped using polymerase chain reaction and mass spectrometry analysis.The SPSS16.0 software was used to compare genotype frequencies and the generalized multifactor dimensionality reduction ( GMDR ) method was applied for gene-gene interaction analyses.Results The results showed that EPHX2 GG genotype might protect against stroke ( OR =0.520, 95% CI 0.288 -0.940, P=0.030).The distribution of CYP3A5 genotypes showed statistically significant differences (χ2 =7.284, P=0.026) between the vulnerable plaque ( AA: 5 cases, AG: 36 cases, GG: 28 cases) and stable plaque ( AA: 26 cases, AG: 77 cases, GG: 122 cases ) groups.Multivariate Logistic regression analysis showed that the GG genotype of CYP3A5 was protective factor for unstable plaques ( OR=0.405, 95%CI 0.178 -0.920, P =0.031 ).Differences in other SNPs did not reach statistical significance between the two groups.The GMDR analysis showed a significant gene-gene interaction between SG13S114 and A6986G, with scores of 10 for cross-validation consistency and 9 for the sign test (P=0.011).The best model for ischemic stroke was found to be SG13S114 AA and A6986G AA.Adjusting for age, hypertension and diabetes, the certain gene-gene interaction predicted a significantly higher risk of cerebral infarction (OR=1.804, 95%CI 1.180-2.759, P=0.006).Conclusions The EPHX2 G860A gene might be linked with the incidence of cerebral infarctions.Only a CYP3A5 gene polymorphism might be associated with carotid plaque instability in patients with stroke.The gene-gene interaction predicts a significantly higher risk of cerebral infarction.There is a 1.804-fold increased risk for ischemic stroke in individuals with these combined genetic factors.

Screening of common deaf genes in pregnant women and prevention of deafness at birth / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the carrier rate for common mutations causing deafness among pregnant women in order to prevent births of deaf children.</p><p><b>METHODS</b>For 893 pregnant women, 2 mL peripheral venous blood was taken and DNA was extracted. A deafness DNA microarray screening was applied to such samples, and DNA sequencing was applied to husbands of women with positive screening results.</p><p><b>RESULTS</b>A total of 40 carriers were detected, with the overall mutation rate being 4.48%. Among such carriers, GJB2 235delC was the most common heterozygous mutation (18 cases) and the mutation rate was 2.02%. GJB2 299A-T heterozygous mutation was detected in 7 cases with a mutation rate of 0.78%. IVS7-2A to G heterozygous mutation was detected in 9 cases with a mutation rate of 1.02%. There were 2 cases carrying GJB3 heterozygous mutation and 2 cases of mitochondrial 12S rRNA heterozygous mutation, with a mutation rate of 0.22%. IVS7-2A>G with GJB3 538C>T double heterozygous mutation was detected in 1 case, and IVS7-2A>G with GJB2 299A-T double heterozygous mutation was detected in another case, with the mutation rate of each being 0.11%. DNA sequencing has failed to find presence of mutations in the same gene in the husbands. The results of neonatal hearing follow-up were all normal.</p><p><b>CONCLUSION</b>Applications of the deaf genes screening in pregnant women may play prove to be valuable for the early detection for neonatal deafness.</p>

Prenatal diagnosis of Down syndrome using cell-free fetal DNA in amniotic fluid by quantitative fluorescent polymersase chain reaction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Amniotic fluid (AF) supernatant contains cell-free fetal DNA (cffDNA) fragments. This study attempted to take advantage of cffDNA as a new material for prenatal diagnosis, which could be combined with simple quantitative fluorescent polymerase chain reaction (QF-PCR) to provide an ancillary method for the prenatal diagnosis of trisomy 21 syndrome.</p><p><b>METHODS</b>AF supernatant samples were obtained from 27 women carrying euploid fetuses and 28 women carrying aneuploid fetuses with known cytogenetic karyotypes. Peripheral blood samples of the parents were collected at the same time. Short tandem repeat (STR) fragments on chromosome 21 were amplified by QF-PCR. Fetal condition and the parental source of the extra chromosome could be determined by the STR peaks.</p><p><b>RESULTS</b>The sensitivity of the assay for the aneuploid was 93% (26/28; confidence interval, CI: 77%-98%) and the specificity was 100% (26/26; CI: 88%-100%). The determination rate of the origin of the extra chromosome was 69%. The sensitivity and the specificity of the assay in the euploid were 100% (27/27).</p><p><b>CONCLUSIONS</b>Trisomy 21 can be prenatally diagnosed by the QF-PCR method in AF supernatant. This karyotype analysis method greatly reduces the requirement for the specimen size. It will be a benefit for early amniocentesis and could avoid pregnancy complications. The method may become an ancillary method for prenatal diagnosis of trisomy 21.</p>

Interactions between 5-1ipoxygenase-activating protein and cytochrome P450 3A5 gene variants significantly increase the risk of cerebral infarction / 中华神经科杂志

Objective To investigate 4 variants single nucleotide polymorphisms (SNPs) of 5-lipoxygenase-activating protein(ALOX5AP) in lipoxygenase pathway and in cytochrome P450 pathway as susceptibility genes for stroke in a southeastern Chinese population,and evaluate the associations between susceptibility genes and cerebral infarction,to find whether gene-gene interactions increase the risk of cerebral infarction.Methods By case-control study,two hundred and ninety-two patients with cerebral infarction and 259 healthy control subjects were included.Eight variants in 5 candidate genes were examined for stroke risk,including the SG13S32 (rs9551963),SG13S42 (rs4769060),SG13S89 (rs4769874),and SG13Sl14 (rs10507391) variants of the ALOX5AP gene,the G860A (rs751141) variant of the soluble epoxide hydrolase (EPHX2) gene,the A1075C (rs1057910) variant of the CYP2C9 *2 gene,the C430T (rs1799853) variant of the CYP2C9* 3 gene,and the A6986G (rs776746) variant of the CYP3A5 gene.Gene-gene interactions were explored using generalized multifactor dimensionality reduction (GMDR)methods.Results There were no statistically significant differences in the frequencies of the genotypes of the 8 candidate genes.The GMDR analysis showed a significant gene-gene interaction between SG13S114 and A6986G,with scores of 10 for cross-validation consistency and 9 for the sign test (P =0.011).These genegene interactions predicted a significantly higher risk of cerebral infarction (adjusted for age,hypertension,and diabetes mellitus;OR =1.804,95％ CI 1.180-2.759,P =0.006).Conclusions A two-loci gene interaction confers significantly higher risk for cerebral infarction.The combinational analysis used in this study may be helpful in the elucidation of genetic risk factors for common and complex diseases.

ALOX5AP and PDE4D gene polymorphisms and ischemic stroke / 国际脑血管病杂志

Cerebral infarction is a polygenic disease caused by genetic factors and environmental factors.The first discovery in the Icelanders is that the ALOX5AP and PDE4D gene polymorphism may be associated with cerebral infarction.So far,many conclusions of foreign studies are still controversial.This article will summarize the research status and the progress of these two genes.