Objective To investigate the prevalence of thyroid diseases in women within 20-week gestation,and to discuss necessity of thyroid diseases screening in women within 20-week gestation.Methods 4986 singleton pregnant women performing prenatal examination in the Maternity and Child Health Care Hospital of Huzhou were recruited into this study.TSH,FT4,and TPOAb levels were detected with ABBOTT ARCHITECT i4000SR.Results ① The median value of TSH rised,the median value of FT4 went down with increase of the gestational weeks.There was significant difference of median value of TSH and FT4 between early and second trimester of pregnancy(P＜0.01).② Rate of abnormal thyroid function was 12.88％,which was higher in the sec ond trimester of pregnancy than that in early pregnancy,and the difference had statistical significance (P＜0.05).③ Positive rate of TPOAb in pregnant women was 11.41％.TPOAb levels were positively correlated with TSH,and no correlation with FT.TSH levels were negatively correlated with FT4.Prevalance of clinical hypothyroidism and subclinical hypothyroidism in TPOAb positive group was significantly higher than that in TPOAb negative group,and the difference had significant difference (P＜0.05).Conclusions Prevalence of thyroid diseases during pregnancy is high.TPOAb is a risk factor and important predictor for hypothyroidism during pregnancy.It is very necessary to perform thyroid diseases screening for pregnant women as early as possible to ensure safety of pregnant women and their babies.

Objective To investigate clinical value of single nucleotide polymorphism array (SNParray) gene chip technique in diagnosis of genetics of recurrent spontaneous abortion (RSA).Methods From January to October 2012,the 26 patients with more than twice of spontaneous abortion in Huzhou Maternal and Child Health Care Hospital were enrolled in this study(RSA group).Meanwhile 20 cases with induced abortion were taken as control group.All aborted tissues were analyzed with conventional cytogenetic karyotyping and SNP-array,respectively.Results Chorionic villus chromosomal examination was successfully done in 19 cases (73％,19/26),which 10 cases were found with chromosomal anomaly,the overall detection rate is 10/19.However,SNP-array analysis was successfully performed in all 26 cases.The overall rate of detection was 100％,and abnormalities were found in 15 cases,which reached the detection rate was 58％ (15/26).Chorionic villus chromosomal examination was successfully done in 16 cases (16/20) in control group,and none of the resluts was chomosomal anomaly; SNP-array analysis was successfully performed in all 20 cases (20/20),and none was found abnormalities.Conclusion SNP-array gene chip technique showed highly accurate feature,which could be used in cytogenetic diagnosis of recurrent spontaneous abortion.

Objective: To explore the genetic basis of a child with idiopathic mental retardation. Methods: Clinical data and peripheral blood sample of the child were collected. Genomic DNA was extracted and subjected to copy number analysis using single nucleotide polymrophism array comparative genome hybridization (SNP-aCGH) and targeted capture and next generation sequencing (NGS). Results: No microdeletion/microduplication were detected by SNP-aCGH. NGS has detected homozygous c. 722delA(p.Asp241fs) variant of the LISN1 gene, which is known to underlie autosomal recessive mental retardation - 27 (MRT 27). Both parents are carriers of the variant, conforming to the autosomal recessive inheritance. Conclusion A novel pathogenic variant of the LINS1 gene has been identified, which probably underlies the MRT 27 in the patient.

Objective: To explore the clinical features and molecular basis for a child featuring infantile epilepsy and developmental disorders. Methods: Clinical data and peripheral blood samples of the child and his parents were collected. The coding regions of genes associated with nervous system development were subjected to target region capture sequencing. Results: The child developed generalized spasm at 3 months and was diagnosed with epilepsy at 6 months of age. He was treated with Depakin but was diagnosed with mental retardation and developmental retardation at 3 years of age. A novel heterozygous c. 3842T>G variant of the SYNE1 gene was detected. His father was found to carry the same variant and had a history of convulsions in infancy but with no mental or developmental anomalies. Conclusion A novel variant of SYNE1 gene was identified in this child, and the prognosis may be poor.

OBJECTIVETo explore the genetic etiology of two fetuses with Dandy-Walker malformation using single nucleotide polymorphism microarray (SNP-array).

METHODSThe fetuses and their parents were subjected to G banding karyotype analysis. The fetuses were also subjected to SNP-array analysis.

RESULTSThe parents of both fetuses showed a normal karyotype. One fetus has a 46,X,?i(X)(q10), while for another conventional cell culture has failed. SNP-array showed that one fetus carried a 6p25.3p25.2 microdeletion, and another carried a Xp22.33p22.2 deletion and a Yq11.221q11 duplication. The abnormal fragments have involved FOXC1, SHOX and STS genes, which are associated with Dandy-Walker malformation.

CONCLUSIONAlteration of 6p25.3p25.2, Xp22.33p22.2 copy numbers probably underlies the Dandy-Walker syndrome in the fetuses. The disorder may be attributed to abnormal expression of FOXC1, SHOX, and STS genes. SNP-array can provide an important supplement for prenatal diagnosis.

Adult ; Chromosome Banding ; Chromosome Deletion ; Dandy-Walker Syndrome ; diagnosis ; genetics ; Female ; Humans ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To provide genetic testing and prenatal diagnosis for a woman with Sheldon-Hall syndrome. METHODS: The woman was subjected to targeted capture and next-generation sequencing for variant of genes associated with skeletal disorders. And the result was verified in her parents and fetus. RESULTS: The woman was found to harbor a c.188G>A variant of the TNNT3 gene, which was also found in her affected mother and the fetus. Her grandmother and grandmother's brother had similar manifestations, which was in line with an autosomal dominant inheritance. The same variant was not found in her father. CONCLUSION The c.188G>A variant of the TNNT3 gene probably underlay the distal joint contracture in this pedigree, based on which prenatal diagnosis was attained.

Objective To investigate the distribution of methyleneterahydrofolate reductase (MTHFR) C677T gene polymorphisms and serum homocysteine (Hcy) levels in pregnant women. Method A total of 2 066 women with singleton pregnancies undergoing prenatal examinations in the Maternity and Child Health Care Hospital of Huzhou from January 2017 to October 2017 were recruited for the study.The MTHFR C677T genotype was detected by PCR-fluorescence probing, and the serum Hcy levels were detected by the cyclic enzyme method. According to the MTHFR C677T genotype detection analysis, the results were divided into the CC-type, CT-type, and TT-type groups. Statistical analyses were performed using the Hardy-Weinberg genetic equilibrium test, chi-square test, variance analysis, and t test. Result Among the 2066 pregnant women, the CC, CT, and TT genotype frequencies for the MTHFR C677T gene were 39.35%,46.52%,and 14.13%,respectively.The Cand T allele frequencies were 62.61% and 37.39%, respectively. The statistical significance values for the Shanxi, Zibo, Shanghai, Suzhou, Shangzhi, Xi'an, Huizhou, and Nanning areas were as follows: χ2=161.999, 166.083; 111.005, 112.517; 416.146, 441.245;14.262,14.23;36.368,35.871;199.498,204.771;19.641,16.377;and 66.79,61.593,respectively;P<0.05. The level of serum Hcy was(7.48±2.20)μmol/L,and the abnormal rate was 3.53%.The level of serum Hcy and the abnormal rate among the 3 genotypes were distributed as follows: TT>CT>CC. The difference was statistically significant(F=120.968, χ2=52.572, P=0.000). Conclusion The distribution of genotype frequencies for MTHFR C667T in 2 066 pregnant women was different in various geographical regions.The level of serum Hcy was associated with the MTHFR C677T gene. Observing MTHFR C677T gene polymorphisms and serum Hcy levels is helpful for monitoring and guiding folic acid supplementation during pregnancy,and establishing reasonable individual health preventive measures.It is an important method to improve the quality of life of the offspring and the family happiness index.

OBJECTIVE: To explore the origin and mechanism of small supernumerary marker chromosomes (sSMC) in three fetuses. METHODS: The three fetuses were predicted to have carried chromosomal abnormalities by non-invasive prenatal testing (NIPT). G-banding chromosomal karyotyping analysis were carried out on amniotic fluid samples of the fetuses and peripheral blood samples from their parents. Single nucleotide polymorphism array (SNP-array) was used to determine the origin, size and genetic effect of sSMCs. RESULTS: In fetus 1, SNP array has detected two microduplications respectively at 4p16.3p15.2 (24.7 Mb) and 18p11.32q11.2 (20.5 Mb) which, as verified by fluorescence in situ hybridization (FISH), have derived from a balanced 46,XY,t(4;18)(p15.2q11.2) translocation carried by its father. Fetus 2 has carried a de novo microduplication of 15q11.2-q13.3 (9.7 Mb). The sequence of SMC in fetus 3 has derived from 21q11.2-q21.1 (8.3 Mb), which was inherited from its mother. CONCLUSION Both NIPT and SNP-array are highly accurate for the detection of sSMC. SNP-array can delineate the origin and size of abnormal chromosomes, which in turn can help with clarification of sSMC-related genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.
Chromosome Duplication/genetics* ; Female ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; Translocation, Genetic/genetics*

OBJECTIVE: To detect mutation of NDP gene in a pedigree affected with Norrie disease. METHODS: Sanger sequencing was used to analyze the NDP gene at Xp11.3. Prenatal diagnosis was performed on amniotic fluid sample after the causative gene was detected. RESULTS: Sanger sequencing has revealed a c.2T>C (p.M1T) missense mutation of the NDP gene in the proband and the fetus. The same variation was not found in ClinVar and HGMD database. CONCLUSION The c.2T>C mutation of the NDP gene probably underlies the Norrie disease in this pedigree.
Blindness ; congenital ; Eye Proteins ; Female ; Genetic Diseases, X-Linked ; Humans ; Nerve Tissue Proteins ; Nervous System Diseases ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Retinal Degeneration ; Spasms, Infantile

PURPOSE: Uridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosynthesis. Recent studies have shown that UCK2 is overexpressed in many types of cancer and may play a crucial role in activating antitumor prodrugs in human cancer cells. In the current study, we evaluated the potential prognostic value of UCK2 in breast cancer. METHODS: We searched public databases to explore associations between UCK2 gene expression and clinical parameters in patients with breast cancer. Gene set enrichment analysis (GSEA) was performed to identify biological pathways associated with UCK2 gene expression levels. Survival analyses were performed using 10 independent large-scale breast cancer microarray datasets. RESULTS: We found that UCK2 mRNA expression was elevated in breast cancer tissue compared with adjacent nontumorous tissue or breast tissue from healthy controls. High UCK2 levels were correlated with estrogen receptor negativity (p<0.001), advanced tumor grade (p<0.001), and poor tumor differentiation (p<0.001). GSEA revealed that UCK2-high breast cancers were enriched for gene sets associated with metastasis, progenitor-like phenotypes, and poor prognosis. Multivariable Cox proportional hazards regression analyses of microarray datasets verified that high UCK2 gene expression was associated with poor overall survival in a dose-response manner. The prognostic power of UCK2 was superior to that of TNM staging and comparable to that of multiple gene signatures. CONCLUSION: These findings suggest that UCK2 may be a promising prognostic biomarker for patients with breast cancer.
Biomarkers ; Breast Neoplasms* ; Breast* ; Dataset ; Estrogens ; Gene Expression ; Humans ; Neoplasm Metastasis ; Neoplasm Staging ; Phenotype ; Prodrugs ; Prognosis* ; RNA, Messenger ; Uridine Kinase*