Result of carrier screening for spinal muscular atrophy among 3049 reproductive-age individuals from Yunnan region / 中华医学遗传学杂志

OBJECTIVE@#To perform carrier screening for spinal muscular atrophy (SMA) among 3049 reproductive-age individuals from Yunnan region and determine the copy number of survival motor neuron (SMN) gene and carrier frequencies.@*METHODS@#Multiplex ligation-dependent probe amplification (MLPA) was used to determine the copy number of exon 7 of SMN1 and SMN2 genes and identify those with a single copy of SMN1 gene. Prenatal diagnosis was performed for couples whom were both found to be SMA carriers.@*RESULTS@#In total 62 SMA carriers were identified among the 3049 subjects, which yielded a carrier frequency of 1 in 49 (2.03%). No statistical difference was found in the carrier frequency between males and females (1.91% vs. 2.30%, P>0.05). Respectively, 1.3% (41/3049) and 0.69% (21/3049) of the carriers were caused by heterozygous deletion and conversion of the SMN1 gene. The average copy number for SMN1 alleles was 1.99. Two couples were found to be both as SMA carriers, for whom the birth of an affected fetus was avoided by prenatal diagnosis.@*CONCLUSION@#No difference was found in the carrier frequency of SMA-related mutations between the two genders in Yunnan region, which was in keeping to an autosomal recessive inheritance pattern. Determination of the carrier frequency for SMA and SMN gene variants may provide a basis for genetic counseling and prenatal diagnosis for the disease.

Discussion on the standard of clinical genetic testing report and the consensus of gene testing industry / 中华医学遗传学杂志

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Advance in clinical application of non-invasive prenatal screening using cell-free fetal DNA / 中华医学遗传学杂志

Non-invasive prenatal screening using cell-free fetal DNA (NIPS) has been integrated into the prenatal health care only in a short span of five years, and the guidelines provided by professional bodies have been continuously updated. The American College of Medical Genetics and Genomics has made a statement on NIPS in July, 2016, suggesting that the NIPS can replace conventional screening for Patau, Edwards and Down syndromes in a continuum of gestational age and for any maternal age, except those who are significantly obese. The scope of target diseases of NIPS are also growing. Meanwhile, pre- and post-test counseling for NIPS has put forward a greater challenge for medical professionals.

Regulatory role of microRNAs in fetal hemoglobin level / 中国病理生理杂志

MicroRNAs (miRs) play an important role in regulating diverse cellular processes.It has been reported that miRs are associated with the formation and maturation of erythrocytes, and the expression of globin genes at post-transcriptional level.Compared with normal human enrythrocytes, various miRs are altered in the patients with thalassemia.These changes also happen in the patients with diverse clinical manifestations.In this paper, we systematically summarized the recent progress about the expression dysregulation of miRs in β-thalassemia and their roles in regulating the levels of γ-globin and fetal hemoglobin.During β-like globin gene expression, miRs directly or indirectly regulate the levels of erythroid-specific transcription factors through post-transcriptional action, such as B-cell lymphoma 11A (BCL11A), myeloblastosis oncogene (MYB), specificity protein 1 (Sp1), Kruppel-like factor 3 (KLF3) and GATA1.These effects subsequently regulate the switch between γ-and β-globin gene expression and affect fetal hemoglobin production.Targeting miRs might be a novel therapeutic strategy for β-thalassmeia.

Genetic analysis and prenatal diagnosis for a pregnant woman with an unbalanced t(1;2), t(6;7) translocation and intellectual disability / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To provide genetic analysis for a pregnant woman with chromosomal translocations and intellectual disability, and to provide prenatal diagnosis for her fetus.</p><p><b>METHODS</b>Routine G-banding was performed to analyze the karyotypes of the woman and her fetus. Copy number variants were determined with array comparative genomic hybridization (array-CGH).</p><p><b>RESULTS</b>The pregnant woman has carried an apparently balanced translocation involving chromosomes 1, 2, 6 and 7, with a karyotype of 46, XX, t(1;2) (p22;p23), t(6;7) (q21;p15). The karyotype of her fetus was ascertained as 46, XY, t(6;7) (q21;p15) mat. Array-CGH has detected a 4 Mb microdeletion at 6q22.1-q22.31 (115 311 507-119 332 956) in both individuals. As the 6q22.1-q22.31 microdeletion may be associated with the main clinical manifestations of the woman, the family decided to terminate the pregnancy. The fetus was male and appeared to have no obvious abnormality.</p><p><b>CONCLUSION</b>Prenatal diagnosis for pregnant women with translocations and mental retardation is a challenging task. Combined application of cytogenetic analysis and array-CGH may facilitate the diagnosis and genetic counseling.</p>

Application of BoBs technique for detecting common chromosome microdeletion and microduplication syndromes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish a strategy for screening and diagnosing common microdeletion and microduplication syndromes among children with idiopathic mental retardation and development abnormalities.</p><p><b>METHODS</b>Potential chromosomal variations among patients with unexplained mental retardation, cardiac anomalies, particular facial features, learning disabilities and other clinical characteristics were detected with bacterial artificial chromosome BACs-on-Beads (BoBs) technique and karyotyping. Positive results were verified with array-based comparative genomic hybridization (Array-CGH).</p><p><b>RESULTS</b>Fifty eight of the 60 patients had a normal chromosome karyotype. Ten patients with microdeletion and microduplication syndromes were detected by BoBs, which included two positive cases identified through chromosome karyotyping. Two patients were respectively diagnosed as Smith-Magenis syndrome and Prader-Willi/Angelman syndrome by BoBs and the results were confirmed by Array-CGH.</p><p><b>CONCLUSION</b>BoBs is capable of detecting chromosome microdeletion and microduplication with high specificity and throughput, which can compensate the shortcomings of conventional cytogenetic technology and will be widely applied for clinical diagnosis.</p>

Analysis on characteristics of fifteen short tandem repeat genetic polymorphisms in Yunnan Han population / 中国免疫学杂志

Objective:To research on the genetic polymorphism distributions of fifteen short tandem repeat ( STR ) loci (D8S1179,D21S11,D7S820,CSF1PO,D3S1358,TH01,D13S317,D16S539,D2S1338,D19S433,VWA,TPOX,D18S51,D5S818, FGA) in Han race of Yunnan. Methods:A total of 313 specimens were collected from the unrelated individuals in Yunnan Han popu-lation. Genome DNA was extracted and amplified by multiplex PCR technique,the PCR products were analyzed by ABI-3130 genetic analyzer capillary electrophoresis detection, collected statistics of each STR loci genotypic frequency, and carried out the Hardy-Weinberg Genetic balance test. Results: No significant deviation from the Hardy-Weinberg Equilibrium was observed ( P>0. 05 ) , the heterozygosity of the fifteen STR loci in Yunnan Han population were found to be 0. 636-0. 901, Probability match was 0. 034-0. 220. Discrimination power of signal STR loci was 0. 780-0. 966, power of paternity exclusion was 0. 336-0. 797, polymorphism information content was 0. 555-0. 860,the combined accumulation discrimination power and exclusion probability for the 15 STR loci in Yunnan Han population were determined to be more than 0. 999 999 99 and 0. 999 998 408. The allele frequency of the 15 STR loci had a similarity compared with other areas in China,but also had a slight regional differences. Conclusion: The 15 STR loci( D8S1179, D21S11,D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818, FGA ) demonstrate high genetic polymorphism in Yunnan Han population, they have a high forensic science application value in paternity testing and individual identification.

Prenatal diagnosis of chromosome abnormalities and nine microdeletion syndromes using both traditional karyotyping and BoBs / 中华妇产科杂志

Objective To evaluate a new prenatal diagnosis model of chromosomal abnormalities and nine microdeletion syndromes by using both traditional karyotyping and a newly-developed rapid prenatal diagnosis technology, BACs-on-Beads (BoBs) technique. Methods From June 2012 to December 2014, 807 pregnant women with high risk after screening or with other indicators, were performed amniocentesis. Traditional karyotyping and BoBs were employed simultaneously for prenatal diagnosis. Results Thirty-two cases with chromosome aneupoidies were successfully detected both by BoBs and karyotyping, including 18 cases of trisomy 21, 6 cases of trisomy 18, 1 case of trisomy 13, and 7 cases with sex chromosome abnormality. All 8 fetuses with chromosome structural abnormalities detected by karyotyping were missed by BoBs;while BoBs contributed more in detection of five microdeletion syndrome cases, including 3 cases of DiGeorge syndromes (two with microduplication and one with microdeletion), one case of Miller-Dieker syndrome, and one case of Wolf-Hirschhorn syndrome. Conclusion Combined use of traditional karyotyping and BoBs, is a rapid and effective prenatal diagnosis model that may enlarge our horizon on chromosomal diseases and should be widely used in future clinical service.

Triple serum tests screening for Down's syndrome in women at second trimester: a meta analysis / 中华围产医学杂志

Objective To explore the value of maternal serum triple markers screening,consisted of AFP (α-fetal protein),β-human chorionic gonadotropin (β-hCG) and free estriol (uE3),for Down's syndrome,in second trimester.Methods We searched published literatures from PubMed,MEDLINE,China National Knowledge Internet (CNKI) and Wanfang Database from January 1990 to August 2014 and articles met the following criteria were collected:(1) The report was of a screening test;(2) The research purpose was to study the efficiency ofAFP,hCG and uE3 (triple markers) screening for Down's syndrome;(3) The research subjects were pregnant women in second trimester;(4) All of the studied cases were confirmed by amniocentesis and chromosome karyotyping;(5) The pregnant outcomes must be available;(6) Each report should have at least one case of Down's syndrome identified;(7) The literature could be retrieved by Science Citation Index or Chinese core periodicals;(8) When assessed by QUADAS (quality assessment of studies of diagnostic accuracy included in systematic reviews) Quality Assessment Scale,the score should be ≥ 8.Information were extracted,including name of the first author,publication time,sample size,sensitivity,specificity,maternal age,gestational age,cutoff value,β-hCG type and others.MetaDiSc 1.4 software was applied for meta-analysis.I2 was used for heterogeneity,and the fixed or random effects model for calculation of the combined sensitivity,specificity,diagnostic odds ratio (DOR) and the 95％CI.The summary receiver operating characteristic (SROC) curve was drawn.Deek's test in Stata Software was used to validate publication bias.Results A total of 49 literatures were recruited in this study with a total sample size of 960 245.Deck's funnel plot analysis showed that the correlation coefficient and the standard error of bias were-1.067 and 3.64 (t=-0.290,P=0.771).The correlation coefficient and the standard error of the slope were 3.578 and 0.26 (t=13.740,P=0.000).The random effects model showed the pooled sensitivity of the 49 literatures was 0.72 (95％CI:0.70 0.74),the pooled specificity was 0.92 (95％CI:0.92-0.93),and DOR was 33.80 (95％CI:25.03-45.65).The area under the SROC was 0.900 7.DOR of younger age group (including three literatures) was 14.38 (95％CI:3.67-56.42) and 26.64 (95％CI:19.49-36.41) for the older age group (two literatures).For two literatures determining the gestational age based on ultrasonography,the DOR was 50.22 (95％CI:26.91-93.71),and DOR was 33.09 (95％CI:17.33-63.19) for those based on last menstrual period in these two literatures.For eight literatures applied the cutoff value of 1:270,12 applied 1:250 and four applied mixed cutoff value,the DOR was 10.94 (95％CI:3.04-39.38),54.34 (95％CI:42.19-70.01) and 36.37 (95％CI:31.19-42.40),respectively.DOR of total β-hCG group (12 literatures) was 22.06 (95％CI:16.46-29.58) and that of free β-hCG group (ten literatures) was 37.15 (95％CI:30.00-46.02).Conclusions Triple regimen of second trimester maternal serum screening for Down's syndrome is much more efficient.The detection rate could be further improved by determination of the gestational age with ultrasound,and application of 1:250 as the risk cutoff value and free β hCG as a screening marker.

Mutations of phenylalanine hydroxylase gene detected in 20 patients with phenylketonuria from Yunnan Province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the mutations of phenylalanine hydroxylase (PAH) gene in 20 phenylketonuria (PKU) patients from Yunnan.</p><p><b>METHODS</b>The 13 exons and the splicing regions of 12 introns of the PAH gene were sequenced to detect mutations in 20 unrelated PKU patients.</p><p><b>RESULTS</b>PAH gene sequencing has revealed 15 types of mutations, in which the most frequently mutation was p.R243Q (30.0%), followed by p.Y356X(10.0%), p.R111X (7.5%), IVS4+2T>A (7.5%) and p.V399V (7.5%). Exons 7, 11, 3 and introns 4, 11 were most frequently involved. Six novel mutations, including c.59A>C, c.60G>C, c.690_691insG, c.1119_1120insT, c.441+2T>A, c.842+4A>T and c.1200+1T>G were detected.</p><p><b>CONCLUSION</b>PAH gene mutations identified in Yunnan are more similar to those of northern China, with R243R being the most common, though there are still certain characteristics for the type and frequency of mutations.</p>

Genetic analysis and prenatal diagnosis of Xp deletion in a family with Duchenne/Becker muscular dystrophy / 中华医学遗传学杂志

OBJECTIVE To delineate a deletional mutation of the Dystrophin gene on the short arm of chromosome X in a family affected with Duchenne/Becker muscular dystrophy. METHODS G-banded karyotyping, multiple ligation probe amplification (MLPA), array-based comparative genomic hybridization(array-CGH) and whole genome exon high-throughput sequencing were employed to delineate the mutation in the family. RESULTS GTG banding has demonstrated deletion of the terminal part of the short arm of chromosome X in the fetus. The same deletion was also found in its mother and maternal grandmother. MLPA analysis has revealed removal of exons 52 to 79 of the Dystrophin gene. A 30 Mb deletion in Xp22.33-p21.1 and a 10 Mb duplication in Xq27.2-q28 were identified by array-CGH and whole genome exon high-throughput sequencing. CONCLUSION The Xp deletion has led to deletion of exons 52 to 79 of the Dystrophin gene in the family. The female carriers also had certain features of Turner syndrome due to the same deletion.

Genetic diagnosis of 154 patients with suspected spinal muscular atrophy and its clinical value / 中华检验医学杂志

Objective To explore the clinical value of genetic diagnosis of SMA,the homozygous deletion of survival motor neuron 1 (SMN1) gene in suspected spinal muscular atrophy (SMA) patients were analyzed in this study.Methods A total of 154 patients suspected with SMA and 20 healthy volunteers were recruited from January 2007 to December 2014 in the Genetic Diagnosis Center of the First People's Hospital of Yunnan Province and the Department of Neurology of the Fourth Affiliated Hospital of Kunming Medical University.Potential deletions in exons 7 and 8 of SMN1 gene were screened by use of polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method in both 154 patients suspected with SMA and 20 healthy volunteers.The frequencies of the deletions in exons 7 and 8 of SMN1 were calculated and statistical analysis of different deletion types among 3 SMA groups was performed with SPSS 13.0 software package.Results Among 154 suspected SMA patients,101 cases with homozygous deletions of exon 7 of SMN1 gene were detected,which accounted 65.6％ (101/154) of the suspected SMA patients.Among the 101 SMA patients,97.0％ (98/101) of the patients with both homozygous deletions of exons 7 and 8 for SMN1 gene and 3.0％ (3/101) of the patients with homozygous deletions of only exon 7 for SMN1 gene were detected.The patient with only deletion of exon 8 for SMN1 gene was notdetected.Four cases with negative results were subjected to be followed-up,but they were characteristic of SMA symptom by clinical re-visit.Thus,total 105 patients were confirmed with SMA,among them,68 were type Ⅰ SMA,27 were type Ⅱ SMA,and 10 were type Ⅲl SMA,which accounted for 64.8％ (68/105),25.7％ (27/105) and 9.5％ (10/105) of the SMA patients,respectively.Type Ⅳ SMA was not observed in these patients.No deletion was detected among 20 healthy volunteers.Conclusions PCR-RFLP assay is a noninvasive,simple,high sensitive and specific method for SMA diagnosis,which can be considered as the first-line genetic test for the suspected SMA patients.It will help to improve the accuracy of clinical diagnosis and the detection rate by strengthening the clinical diagnostic criteria and re-evaluating the suspected patients after negative genetic diagnosis.

Study of glycemic fluctuation impact on angiopoietin-2 and endoplasmic reticulum stress in type 2 diabetes complicated with acute phase of acute coronary syndrome / 中华内分泌代谢杂志

Objective To investigate the changes in angiopoietin 2 and endoplasmic reticulum stress,and the prognosis of acute phase of coronary syndrome (ACS) in type 2 diabetic patients with glycemic fluctuations.Methods Seventy-eight cases of consecutive diabetic patients with ACS within 7 days were enrolled.Another 78 cases of non-diabetic patients with ACS were selected as control.Risk assessment with global acute coronary events (GRACE) score in patients with ACS,dynamic blood glucose monitoring system (CGMS) for three days,realtime PCR analysis of angiopoietin-2,within the reticulum stress-related heavy chain binding protein (Bip),inositol kinase demand Ⅰ (IREI),endoplasmic reticulum class should PKR kinase (PERK),oxygen-regulated protein 150 (ORP150),activating transcription factor 6 (ATF6),X-box binding protein 1 (XBP1)mRNA expression change,phosphorylation of eukaryotic translation initiation factor 2oα (p-eIF2α) by western blotting angiopoietin-2,parameters were compared between the two groups.Correlation analysis with GRACE score ; while angiopoietin-2 parameters and glycemic fluctuation,endoplasmic reticulum stress-related genes correlation analysis were made.Results (1) ACS group average daily blood glucose fluctuations(MAGE),mean absolute difference daytime blood glucose (MODD),and postprandial blood glucose fluctuation (MPPGE) and the maximum amplitude of glycemic excursions (LAGE) were significantly higher [MAGE(5.13 ± 1.19) vs (3.19 ± 0.55) mmol/L,MODD (2.59 ± 0.72) vs (1.72 ± 0.63) mmol/L; MPPGE (3.51 ± 1.01) vs (2.58 ± 0.55) mmol/L and LAGE (7.75 ± 2.39) vs (4.34 ± 0.85) mmol/L,all P＜0.05].(2)In ACS group angiopoietin-2,endoplasmic reticulum associated genes Bip,IREI,PERK,ORP150,ATF6,XBP1,and monocyte chemoattractant protein 1 (MCP-1) mRNA expression levels as compared with the control group were statistically significant(all P＜0.05) ; Angiopoietin-2,protein p-eIF2α were higher(P＜0.05).(3) In the ACS group with pearson correlation analysis,angiopoietin-2 and MAGE,LAGE,MPPGE correlation (r =0.432,0.279,0.386,all P＜0.05),Bip and MAGE,LAGE,MPPGE correlation(r =0.783,0.589,0.887,all P＜ 0.05) ; IREI and MAGE,LAGE,MPPGE,MODD correlation (r =0.567,0.783,0.569,0.823,all P＜0.05) ; PERK and MAGE,MPPGE,MODD correlation(r =0.687,0.902,0.709,all P＜0.05) ; ORP150 and MAGE,LAGE,MPPGE,MODD correlation(r=0.779,0.871,0.775,0.689,all P＜0.05) ; ATF6 and MAGE,LAGE,MPPGE,MODD correlation(r =0.873,0.675,0.893,0.884,all P＜0.05),while XBP1 with no correlation with glycemic fluctuations (P＞0.05).(4) The endoplasmic reticulum stress gene was related to MCP-1 and blood glucose fluctuation parameters.(5) Multiple Logistic regression analysis revealed that LAGE,MPPGE,Bip,IREI,PERK,ORP150,ATF6 were risk factors affecting angiopoietin-2,and angiopoietin-2,ages,MAGE,homeostasis model assessment for insulin resistance,Bip,ATF6 were risk factors affecting GRACE.(6) The ejection fractions of the ACS patients showed negative correlation with MAGE and LAGE,multiple linear regression analysis showed that age,HOMA-IR,Ang-2,and MAGE,Bip,ATF6 established the linear regression relation with ejection fraction.Conclusion Glycemic fluctuations cause angiopoietin-2 to rise and lead to increased endoplasmic reticulum stress and affect the prognosis of diabetic patients with ACS.

Investigation of thyroid function parameters in subclinical hypothyroid women treated with levothyroxine during pregnancy / 中华内分泌代谢杂志

Subclinical hypothyroidism during pregnancy is associated with some adverse outcomes during maternal pregnancy.The present study investigated thyroid function parameters measured by electroehemiluminescence (ECL) immunoassays in subclinical hypothyroid women treated with levothyroxine (L-T4) during pregnancy.The results showed that in evaluating thyroid function with ECL immunoassays during replacement with L-T4,determination of serum TT4 appears to have a closer correlation with TSH and may better reflect the effìcacy of treatment.

A study on gene mutation spectrums of α- and β-thalassemias in populations of Yunnan Province and the prenatal gene diagnosis / 中华妇产科杂志

Objective To investigate mutation spectrums of α- and β-haemoglobin genes in thalassemia patients and carriers in Yunnan province,and to establish procedures on prenatal gene diagnosis.MethodsTotally 10 033 counseling couples and pregnant women,and 22 cases of children with moderate or severe thalassemia were recruited from 5 parts of Yunnan Province,middle,western,eastern,southern and northern areas, during July 2009 to July 2011.Medical records, including results of haemoglobin electrophoresis,blood routine examination,and gene diagnosis of subjects were collected and saved in an database in Excel software by the Key Laboratory for Birth Defects and Genetic Diseases.Using multiple gap-PCR and PCR-reversed dot blotting kits, DNA samples collected from 1077 cases of haematological positive thalassemia patients and carriers were tested to determine common mutations of the α-or β-haemoglobin genes.The codon regions of haemoglobin genes were sequenced by the Sanger sequencing in cases that the mutation tests were negative.Mutation spectrums of α- and β-haemoglobin genes were concluded.Prenatal gene diagnosis was offered to fetuses who had risk of thalassemia major.Results( 1 ) In 1077 cases of haemological screen positive subjects,deletions and mutations of α-haemoglobin gene were tested in 119 subjects among 347 cases suspected as α-thalassemia patients and carriers.Five kinds of deletions and mutations on α-haemoglobin gene were found.In 104 subjects,four kinds of common deletions and mutations onα-haemoglobin gene were determined:--SEA, -α3.7, αCS α,-α4.2.Other 14 subjects were double heterozygotes with haemoglobin H disease and severe α-thalassemia phenotypes.A rare mutation of insertion and deletion in α2 haemoglobin gene intron,α301-24-301-23 indel,was found in one carrier subject.(2)In 1077 cases of haemological screen positive subjects,deletions and mutations of β-haemoglobin gene were tested in 297 subjects among 730 cases suspected as β-thalassemia patients and carriers.Sixteen kinds of β-haemoglobin gene mutations were found,including 7 cases of rare abnormal haemoglobinopathy patients with β-haemoglobin gene mutations.In one case with β + phenotype patient,the Codon 5 (-CT)mutation at β-haemoglobin gene was found (firstly reported in China ). (3) Three fetuses with high riskS of α-thalassemia were accepted for prenatal diagnosis.One case of Hb Bart's hydrops syndrome fetus with the genotype --SEA/--SEA,and one case of mild α-thalassemia fetus with the genotype αCS α/αα were found.Another one fetus was found with normal α-haemoglobin.In 6 fetuses accepted for prenatal diagnosis due to high risks of β-thalassemia,one case of β-thalassemia major with the genotype CD17( A→T)/-28 (A→G) was found,3 fetuses were heterozygote carriers,and 2 fetuses had normal genotypes without mutations found in their parents.Medical terminations for 2 fetuses with severe thalassemia were made according to the choice of pregnant women.Other 7 pregnancies continued to term.Anemia or growth retardation was not found in the 7 infants when following up after given-birth 6 to 12 months.Conclusions The mutation spectrums of α- and β-haemoglobin genes of thalassemia patients and αarriers.in Yunnan province are special,in which β-haemoglobin gene exits more polymorphism in the mutation spectrum.Carrier screening in pregnant women,and offering prenatal gene diagnosis to the high risk pregnancies should be an efficient strategy to prevent thalassemia major.

Levothyroxine dosage and related factors in the treatment of pregnant women with subclinical hypothyroidism / 中华内分泌代谢杂志

Objective To study the levothyroxine doses and related factors in the treatment of pregnant women with subclinical hypothyroidism (SCH).Methods Fifty-six pregnant women with SCH (diagnosed before 12 weeks of gestation) were recruited and divided into 2 groups according to the baseline TSH levels,SCH group 1 (2.5 mIU/L ≤ TSH ≤ 5.0 mIU/L,n =24) and SCH group 2 (TSH＞5.0 mIU/L,n =32).Thyroid autoantibodies [thyroid peroxidase antibody(TPOAb) and thyroglobulin antibody(TGAb)] were detected.All the subjects were treated with levothyroxine and the doses were adjusted according to the TSH level.The therapeutic target was to keep the TSH levels under control,0.3 to 2.5 mIU/L for the first trimester and 0.3 to 3.0 mIU/L for the second and third trimesters.Results There was a positive correlation between the levothyroxine doses and baseline TSH levels (r =0.533,P＜0.01) in pregnant women with SCH.A significant difference in the levothyroxine doses between SCH group 1 and SCH group 2 was found [(0.583 ± 0.341) vs (0.961 ± 0.405) μg/kg,t =-3.695,P＜ 0.01].The levothyroxine doses in SCH group 2 were 64.84％ higher than those in group 1.There was a significant difference in the levothyroxine doses between thyroid autoantibody negative and positive subjects [(0.680 ± 0.370) vs (0.918 ±0.440) μg/kg,t =-2.197,P =0.032].The levothyroxine doses in thyroid autoantibody positive subjects were 35 ％ higher than those in the negative subjects.In addition,there was a significant difference in the levothyroxine doses between subjects with negative and positive thyroid autoantibody [(0.421 ± 0.192) vs (0.720 ± 0.385)μg/kg,t =-2.331,P =0.029] in SCH group 1.While in SCH group 2,the difference did not reach statistical significance.Conclusion The baseline TSH levels and status of thyroid autoantibodies may affect the levothyroxine dosage in pregnant women with SCH.

Study on key techniques and intervention in reducing birth defects / 中华妇产科杂志

ObjectiveTo investigate key techniques and intervention in reducing birth defects. Method Down's syndrome (DS), trisomy-18 (Edwards syndrome, ES), neural tube defects (NTD), Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), thalassemia, and glucose-6-phosphate dehydrogenase deficiency (G6PD) were chosen as target disease. From Jan. 2007 to Dec. 2009, the condition of intake folie acid were investigated in 5004 pregnant women in Panlong District and Wuhua District of Kunming City. All of the 27 660 pregnant women undergoing prenatal examination were enrolled into the study from the First People's Hospital of Yunnan Province, the Second People's Hospital of Yunnan Province, the First People's Hospital of Qujing City, the Second People's of Qujing City, Qujing Women and Children's Hospital, People's Hospital of Lincang City, Kunming Maria Women's Hospital, Maternal and Infant's Care Unit of Panlong District of Kunming City, Maternal and Infant's Hospital of Dali City. The screening was performed on serum of those pregnant women at 8 -20 +6 gestational weeks. Prenatal cytogenetic analysis and fetal ultrasonogrspy were performed on the high risk or indicated women after genetic counseling. DNA analysis was administered on those women with family or childbearing history of DMD,SMA,thalassemia,orG6PD. Outcomeof pregnancywasfolloweduptoevaluatetheeffectof intervention. ResultsApproximately 30. 10％ (1506/5004) of pregnant women were administered by oral folic acid during perinatal period. Two thousand three hundred and thirteen women with high risks of DS,ES, or NTD fetuses were observed among 27 660 undergoing maternal serum screening. Two thousand and ninety-six pregnant women including two twins pregnant women were performed cytogenetic analysis. Other 67 pregnant women at high risk of DMD, SMA, thalassemia, and G6PD accepted genetic counseling and prenatal gene analysis. Two thousand one hundred and sixty-three pregnant women (2165 fetuses) underwent prenatal examination. One hundred and two cases chromosome abnormalities, 17 cases NTD, 4 cases DMD, 1 cases α-thalassemia major were found. All of the 91 fetuses with major birth defects were terminated after genetic counseling. Another affected DS fetus in a twin pregnancy dead intrauterine at 24 gestational weeks. Thirty-two women bearing fetuseswithbalancedtranslocations orinversionscontinuedtheir pregnancies. Totally 2071 normal term fetuses were born in the prenatal diagnosis group. Two fetuses with normal chromosome were lost within 1 week after amniocentesis. Four affected DS fetuses were born from their high risk mothers who refused further prenatal diagnosis service. In a random sampling follow-up cohort of 5000 mothers at low risk, none of affected child suffering target diseases was found. The DS detection rate of maternal serum screening was 84％ (27/32), with the false positive rate was 6. 153％ (1702/27 660).ConclusionsFolic acid intake before conception and in the first trimester would reduce the risk of birth defects, only 1/3 reproductive women took folie acid actively. Maternal serum screening could effectively detect high risk of DS, ES and NTD. The genetic counseling is critical in women at high risk or who had family history of inherited disorders. The prenatal screening and diagnosis combined with routine obstetric care could reduce the incidence of major birth defects, which should become prenatal care strategy in our country.

Second trimester maternal serum screening for Down's syndrome in women of advanced maternal age: a multi-center prospective study / 中华妇产科杂志

Objeetive To evaluate the performance characteristics of the second trimester double test for the detection of fetal Down's syndrome(DS)in women of advanced maternal age(AMA).Methods We undertook a prospective nation-wide multi-centered study and chose alpha-fetoprotein(AFP))and free β-subunit of human chorionic gonadotrophin(free β-hCG)as the serum markers.Between May 2004 and September 2006,12 centers participated in the collection and analysis of maternal serum AFP and free β-hCG.Patients with an iuereaged risk of DS(≥1/270)wero offered generic sunniocentesis.Follow up of the outcome of all pregnancies was obtained.Patients were divided into two groups,the AMA group and the non-AMA group and the screening efficiency Was evaluated in beth groups.Results A total of 66 132 singleton pregnancies were included in the study.and there were 36 10(5.46%)AMA women.The median maternal age of AMA women was 36.8years(35-47 years).At a cut-off of 1/270,in the AMA group,the number of positive cases screened was 727 and 22 cases of fetal DS were detected:the number of negative cases screened was 2883,and no fetal DS was found.In the non-AMA group,the number of positive cases screened was 4743 and 69 cases of fetal DS were detected:the number of negative cases screened was 57 779,and 6 cases of fetal DS were diagnosed postnatally.In AMA group,the detection rate(DR),false positive rate(FPR)and odds of being affected given a positive result(OAPR)were 100%,19.7%and 3.0%respectively.In the non-AMA group,the DR,FPR and OAPR were 92.0%.7.5%and 1.5%respectively.Conclusion The double-marker test using AFP and free β-hCG is an effective screen strategy for second-trimester detection of Down syndrome in AMA women.

Second trimester maternal serum screening for Down's syndrome in mainland China :a multi-center prospective study / 中华妇产科杂志

Objective To evaluate the performance characteristics of the second trimester double-marker test for the detection of fetal Down's syndrome in mainland China. Methods This prospective national multi-centered study used alpha-fetoprotein (AFP) and free β-subunit of human chorionic gonadotrophin( free β-hCG)as the serum markers. From May 2004 to September 2006, 11 centers participated in the collection and analysis of maternal serum AFP and free β-hCG between 14 and 20+6 weeks of pregnancy. The screening results were calculated using the standard algorithm based on the standard database provided with the analytic software. Patients with an increased risk of Down's syndrome pregnancy (≥1/270) were offered genetic anmiocentesis. Outcomes of all pregnancies were obtained.Results A total of 66 132 singleton pregnancies were included in the study. The median maternal age was 27 years. At a cut-eft of 1 in 270, the detection rate (DR) based on a Caucasian database was 72% corresponding to a false positive rate (FPR) of 5%, and the DR based on the Chinese database was raised to 76% corresponding to an FPR of 5%. Conclusion The double-marker test using AFP and free β-hCG is an effective screen strategy for second-trimester detection of fetal Down's syndrome in mainland China. Ethnic variance exists between the Caucasian and Chinese populations. The accuracy of screening is increased by the use of race-specific medians.

Detection of Chromosome 6 Aberration in Lung Carcinoma Using Fluorescence in Situ Hybridization(FISH) / 医学研究杂志

Objective To study the relationship between chromosome aberration and the pathogenesis,development and prognosis of lung carcinoma. Methods Tissue speciments from 30 cases of lung carcinoma and 10 cases of normal lung tissue were detected using FISH with chromosome 6 probe,respectively. Results All of the 30 cases of lung carcinoma were found chromosome 6 aberration,involved monosomy,trisomy,and even heptasomy.But there was no chromosome 6 aberration found in normal lung tissues.The significant difference was between these two groups. Conclusion Chromosome 6 aberration may occur in the early stage of lung carcinoma,which may closely relate with the process of pathogenesis,development of lung carcinoma.The chromosome 6 aberration may have the significant association with clinical phase and pathological differentiation among the patients.