Prenatal diagnosis indications and pregnancy outcomes and its impact factors in 1 372 pregnant women with fetal sex chromosome aneuploidy / 中华围产医学杂志

Objective:To analyze the indications for prenatal diagnosis and summarize the pregnancy outcomes and its influencing factors of pregnant women with fetal sex chromosome aneuploidy (SCA).Methods:This study retrospectively enrolled 1 372 fetuses prenatally diagnosed with SCA in Medical Genetics Center of Guangdong Women and Children Hospital from January 2013 to December 2021. The relationship between prenatal diagnosis indications and SCA as well as between ultrasound abnormalities, pregnancy outcomes and SCA types were analyzed by Chi-square test and trend Chi-square test. Results:The most common prenatal diagnosis indication was abnormal non-invasive prenatal testing (NIPT) (61.6%, 845/1 372). The most common SCA type was 47,XXY in cases with indications of abnormal NIPT and advanced maternal age, mosaic in cases with high or borderline risk of Down syndrome, and 45,X in cases with increased nuchal translucency or cystic hygroma. Of 1 372 pregnant women with fetal SCA, 17 were lost to follow-up, seven had intrauterine fetal death, and 1 348 (98.3%) were followed up for pregnancy outcomes including 36.3% (489/1 348) continued pregnancies and 63.7% (859/1 348) terminations. Pregnancy termination rates decreased sequentially in pregnant women carrying fetuses with 45,X, 47,XXY, mosaic, 47,XXX and 47,XYY [99.2% (247/249), 74.5% (307/412), 67.8% (156/230), 36.6% (86/235) and 28.4% (63/222), χ2trend=352.76, P<0.001]. There was no significant difference in pregnancy termination rates among the cases with different mosaic mutations (all P>0.05). The pregnancy termination rate was higher in fetuses with SCA complicated by ultrasound structural abnormalities than in those without ultrasound abnormalities and those with ultrasound soft markers [91.5% (182/199) vs 57.1% (535/937) and 67.0% (142/212), χ2 were 83.68 and 36.85, both P<0.001]. Moreover, the pregnancy termination rate in fetuses with SCA complicated by ultrasound soft markers was higher than those without ultrasound abnormalities ( χ2=7.13, P<0.05). Conclusions:NIPT abnormality is the most common indication for prenatal diagnosis of SCA. The types of SCA and ultrasound findings are important factors determining whether the pregnancy would be continued or not.

Consensus on technological standards for non-invasive prenatal screening of pathogenic copy number variations by high-throughput sequencing of maternal plasma cell-free DNA / 中华医学遗传学杂志

Genomic disorders caused by pathogenic copy number variation (pCNV) have proven to underlie a significant proportion of birth defects. With technological advance, improvement of bioinformatics analysis procedure, and accumulation of clinical data, non-invasive prenatal screening of pCNV (NIPS-pCNV) by high-throughput sequencing of maternal plasma cell-free DNA has been put to use in clinical settings. Specialized standards for clinical application of NIPS-pCNV are required. Based on the discussion, 10 pCNV-associated diseases with well-defined conditions and 5 common chromosomal aneuploidy syndromes are recommended as the target of screening in this consensus. Meanwhile, a standardized procedure for NIPS-pCNV is also provided, which may facilitate propagation of this technique in clinical settings.

Detection of copy number variations for chromosome non-numerical abnormality with non-invasive prenatal testing: clinical analysis of 205 cases / 中华围产医学杂志

Objective:To evaluate the clinical value of non-invasive prenatal testing (NIPT) in detecting copy number variations (CNVs).Methods:There were 37 845 pregnant women undergoing NIPT in Guangdong Women and Children Hospital from January 1, 2015 to September 1, 2018, of which 205 with CNVs were detected in addition to chromosome numerical abnormality and retrospectively analyzed. Among the 205 cases, 137 received invasive prenatal diagnosis. Pregnant outcomes were followed up and the efficiency of NIPT in detecting CNVs was analyzed by descriptive statistical analysis.Results:The detection rate of NIPT for CNVs was 0.54% (205/37 845). Among the 137 cases undergoing invasive prenatal diagnosis, 110 showed normal karyotype, 27 with abnormal including two having CNVs that were inconsistent with NIPT findings and 25 with consistent results. The positive predictive value, sensitivity and specificity of NIPT for CNVs were 18.2%(25/137), 100.0%(25/25) and 99.7%(37 625/37 737), respectively. Among the 27 pregnant women with positive findings in prenatal diagnosis, five were lost to follow-up; eight terminated their pregnancies; 14 gave birth to alive baby with normal phenotype. While among the 110 pregnant women with negative results in prenatal diagnosis, 87 delivered full-term neonates including two having patent foramen ovale and 85 with normal phenotype; three gave birth prematurely; one terminated pregnancy at 28 +2 gestational weeks due to preeclampsia; two had inevitable abortion; two requested termination and 15 were lost to follow-up. Conclusions:Routine NIPT has high performance in screening CNVs but those pregnant women with positive NIPT results should be counseled after referring to their invasive prenatal diagnosis results, ultrasound scan and clinical information.

A consensus recommendation for the interpretation and reporting of copy number variation and regions of homozygosity in prenatal genetic diagnosis / 中华医学遗传学杂志

Chromosomal microdeletions and microduplications have been proven to be a significant proportion of genetic factors underlying birth defects. Chromosomal microarray analysis (CMA) and next generation sequencing-based copy number variation (CNV-seq) assay have been recommended as first-tier tests for prenatal evaluation of disease-causing CNV across the genome. With the broad application of such technologies in prenatal genetic diagnosis, there is a needed to enhance the consistency in interpretation and reporting of CNV results in clinical laboratories across China. In addition, a standard guideline for prenatal analysis and reporting of regions of homozygosity (ROH) is also required. To assist the classification, interpretation and reporting of CNV/ROH, the following recommendations have been developed, which may enhance a standard application of CMA/CNV-seq techniques in prenatal genetic diagnosis.

The value of noninvasive prenatal screening for the detection of fetal chromosome 16 aneuploidy / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal screening (NIPS) for the detection of fetal chromosome 16 aneuploidy through multi-method verification and follow-up of pregnancy outcomes.@*METHODS@#From January 2016 to December 2017, 7972 pregnant women with singleton pregnancies accepted the NIPS test after 10th gestational week with informed consent. Those with fetal chromosome 16 abnormality suggestive by the NIPS test were subjected to prenatal diagnosis including chromosomal karyotyping and chromosomal microarray analysis (CMA).@*RESULTS@#Of the 7972 pregnant women tested by NIPS, 16 (0.2%) were predicted to have fetal chromosome 16 abnormality. The average age of the 16 pregnant women was 33.5 ± 5.24, and the average gestational week was 19.88±2.47. Chromosomal karyotyping verified that 3 fetuses had mosaicisms and 1 carried pericentric inversion of chromosome 9, which yielded a positive predictive value (PPV) of 18.8%. CMA has detected 7 fetuses with genomic abnormalities, which yielded a PPV of 43.8%. Eleven of the 16 women (68.8%) have given birth to healthy babies.@*CONCLUSION@#For pregnant women with a high risk of chromosome 16 aneuploidy suggested by NIPS, the prognosis of fetus should be evaluated by multiple methods. Compared with conventional karyotyping analysis, molecular methods such as CMA are far superior.

Long-term adverse effects of preeclampsia on offspring / 中华围产医学杂志

An adverse intrauterine environment due to preeclampsia can not only lead to premature birth,low birth weight and fetal intrauterine distress,but also have long-term impacts on the fetus,such as increasing their susceptibility to metabolic,cardiovascular and neurological disorders.It also increases the risk of preeclampsia in female offspring.Researches focusing on the long-term effects of preeclampsia on the future generation is helpful to understand the pathophysiological mechanism of preeclampsia and to provide timely interventions in early life to reduce the occurrence of chronic diseases in later life.

Application of non-invasive prenatal genetic testing in prenatal anomaly index screening / 中华检验医学杂志

Objective@#To evaluate the value of non-invasive prenatal testing (NIPT) in pregnancies with anomaly in prenatal screening. @*Methods@#This was a retrospective study of 2 837 singleton pregnancies who performed NIPT indicated by isolated anomaly in prenatal screening at Guangdong Women and Children Hospital between November 2014 and August 2016. All pregnancies were divided into 3 groups by single indication: advanced maternal age ( AMA, ≥35), abnormal multiples of the median (MoM) in standard screening, increased nuchal translucency thickness (NT, 2.5-3.0 mm). High risk results were verified by prenatal diagnosis. Low risk cases were followed by a 22-26 week anatomical ultrasound examination. All of the cases were followed up and the performance of NIPT for every single indication was evaluated. @*Results@#There were total of 2 837 pregnant women who underwent NIPT. Twenty-five of 2 448 pregnancies indicated by AMA had high risk results, among which 17 were confirmed by invasive genetic testing, except 1 case rejecting prenatal diagnosis. In 351 pregnant women with abnormal MoM, NIPT found 3 cases of sex chromosome aneuploidies (SCA) and 2 of them were validated by invasive prenatal diagnosis. Increased NT group included 38 cases, NIPT found 1 case of trisomy 21 which was consistent with karyotype analysis. For common aneuploidies and SCA, the performance of NIPT in the pregnant women who indicated by AMA, abnormal MoM and increased NT were as the follows: the sensitivity were 17/17, 2/2 and 1/1 respectively, the specificity were 99.7% (2 423/2 431), 99.7% (348/349) and 100%(37/37), the positive predictive value were 68% (17/25), 2/3 and 1/1, the negative predictive value were 100% (2 423/2 423), 100% (348/348) and 100% (38/38), respectively. By follow-up survey, a total of 8 cases of abnormal fetus were recorded in NIPT low-risk women, including 5 cases of termination of pregnancy due to abnormal ultrasound findings, 2 cases of abortion as a result of severe obstetric complications and 1 case of stillbirth. @*Conclusions@#To the pregnant women who indicated by advanced maternal age, abnormal MoM and increased NT (2.5-3.0 mm), NIPT had satisfactory performance for common aneuploidies, and also had potential value for SCA, resulting in a significant reduction in diagnostic procedures. However, for NIPT low-risk pregnancies, routine antenatal examination and anatomical ultrasound detection would be highly necessary to avoid missing abnormal fetuses.(Chin J Lab Med, 2018, 41: 509-513)

Application of suspension array technology for the genetic diagnosis of non-syndromic hearing loss / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of suspension array technology (SAT) for the genetic diagnosis of non-syndromic hearing loss (NSHL).</p><p><b>METHODS</b>Three hundred and sixteen NSHL patients were simultaneously tested by SAT targeting 20 hotspot mutations within 4 common pathologic genes among the Chinese population as well as 9 deafness gene mutation detection kits. The results of the two approaches were validated by Sanger sequencing.</p><p><b>RESULTS</b>Among the 316 patients, 161 were found to carry a mutation by SAT. Sixty five patients have carried homozygous or compound heterozygous mutations, which yielded a mutation rate of 50.9% and a diagnostic rate of 21.2%. Seventy three patients were found to be carriers by the 9 deafness gene mutation detection kits. These included 34 patients carrying homozygous or compound heterozygous mutations, which yielded a mutation rate of 23.1% and diagnostic rate of 11.4%. Above results were consistent with those of Sanger sequencing.</p><p><b>CONCLUSION</b>SAT is a simple, rapid and accurate method featuring high detection rate for common mutations related to deafness among the Chinese population and has provided an effective means of genetic testing for hereditary deafness.</p>

Application of chromosomal karyotyping analysis and array CGH for fetal abnormalities detected by ultrasonography / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of chromosomal karyotyping and array-based comparative genomic hybridization for the diagnosis of fetus with abnormalities detected by ultrasonography.</p><p><b>METHODS</b>Umbilical cord blood samples were derived from 1 603 pregnant women. The samples were cultured for routine G-banding karyotype analysis. Among these, 792 samples have further subjected to array CGH analysis.</p><p><b>RESULTS</b>Among the 1 603 fetuses, 117 (7.30%) were found with chromosomal abnormalities. These included 72 numerical aberrations and 45 structural abnormalities, which respectively accounted for 4.49% and 2.81% of all cases. For those <35 years and ≥ 35 years, a significant difference has been found in terms of fetal chromosomal abnormalities (chi-square is 30.687, P< 0.01). And there was also a significant difference between those with isolated, two or multiple ultrasonographic markers (chi-square is 85.50, P< 0.01). Among 736 fetuses with a normal karyotype, array CGH has detected 17 (2.31%) with a microdeletion or microduplication.</p><p><b>CONCLUSION</b>Karyotype analysis and array CGH should be offered to all fetuses with ultrasonography detected anomalies regardless the number of markers.</p>

The effect of occupational and environmental factors on the pregnancy for Down's syndrome / 中国职业医学

OBJECTIVE: To investigate the influence of occupational and environmental factors on the pregnancy for Down's syndrome. METHODS: By systematic sampling method,97 pregnant women who had been diagnosed as Down's syndrome by Giemsa staining on fetal chromosomes in chorionic villus sampling,amniocentesis,or umbilical cord blood sampling were selected as the case group,while 373 non-Down's syndrome pregnant women after same examinations during the same period in the same hospital were selected as the control group. The history of exposure before pregnancy to occupational and environmental factors was analyzed. RESULTS: The pregnant women aged over 35 years had higher risk of Down's syndrome than those aged under 35 years( P < 0. 01). The pregnant women with occupational exposure to organic solvents containing benzene had higher risk of Down's syndrome than those without occupational exposure history to hazardous substances( P < 0. 01). The pregnant women using estrogenic drugs before pregnancy or during early pregnancy had higher risk of Down's syndrome than those without drug use( P < 0. 05). The pregnant women living in newly-decorated houses or using the new furniture had higher risk of Down's syndrome than those without new decoration( P < 0. 01). The pregnant women with pre-pregnancy intake of folic acid had lower risk of Down's syndrome than those without any intake of folic acid supplement( P < 0. 05). CONCLUSION: The age,occupational exposure to benzene solvents and taking estrogenic drugs were the major leading factors of development of Down's syndrome.

Application of Next-Generation Sequencing in Detection of Mutation Gene in ZMPSTE24 in Prenatal Diagnosisa Chinese Pedigree with Pathological Chorioamniotic Membrane Separation / 中山大学学报(医学科学版)

[Objective] To describe a case of a rare,novel mutation causing recurrent chorioamniotic membrane separation in a Chinese family with combined next-generation sequencing (NGS) and Sanger sequencing.[Methods] For the affected fetus,potential mutation were detected by the conbinedcombined next-generation sequencing (NGS) and Sanger sequencing.And the prenatal diagnosis were identified by Sanger sequencing.[Results] A frameshifting mutation c.1389_1390delAG (inherited from mother),and a missense mutationc.1006 G ＞ C (inherited from mother) have been identified in the affected fetus (the second pregnancy).The prenatal diagnosis of the third fetus turns out to be a carrier,the mutation was inherited from father.[Conclusions] We describe a novel mutation in gene ZMPSTE24,which was considered with mandibuloacral dysplasia with type B,and that may be the cousecoursecausing of recurrent chorioamniotic membrane separation.This rare mutation constitutes an additional heterogeneous defect causing chorioamniotic membrane separation.And the conbinedcombined next-generation sequencing (NGS) and Sanger sequencing allows high resolution characterization of novel mutions that are not readily detected by present methods.

Establishment of a screening method for AZF microdeletions by capillary technology and a clinical trial / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish an accurate, fast and simple screening method for AZF microdeletions using capillary technology and use it for clinical testing.</p><p><b>METHODS</b>For each pair of primers, the 5' end of either forward or reverse primer was labeled with a FAM, JOE or TAMRA fluorescence dyes to establish multiplex quantitative fluorescence PCR systems for the establishment of a screening method of Y chromosome AZF microdeletions by capillary technology. The detection of Y chromosome AZF microdeletion was carried out on 725 cases of non-obstructive azoospermia, oligospermia or asthenospermia.</p><p><b>RESULTS</b>A screening method for Y chromosome AZF microdeletions using capillary technology was established. Thirty eight cases of AZF microdeletions were found among 725 cases of non-obstructive azoospermia, oligospermia or asthenospermia, which gave a deletion rate of 5.24%. Y chromosomal microdeletions were found in 8.62% of the azoospermia group, 6.75% of the oligozoospermic group, and 2.23% of the asthenospermia group.</p><p><b>CONCLUSION</b>An accurate, fast and simple screening method of Y chromosome AZF microdeletions by capillary technology has been established, which may have an important clinical value.</p>

Finite element method for analyzing the stress distribution of acetabulum under different loads / 中国组织工程研究

BACKGROUND:The hip is a complicated structure and irregular in shape. It is hard to measure stress distribution and transmission. OBJECTIVE:To establish a three-dimensional finite element model of the hip joint and upper femur, and analyze the stress distribution and transmission characteristics of the acetabulum region under different loads, and explore mechanics mechanism of hip fracture based on CT data. METHODS:The three-dimensional finite element hip and femur model were reconstructed in Mimics 14.0 based on the CT data of a healthy adult man. After dividing mesh, assigning material and transforming into finite element model, the stress distributions of anterior wal , the top, and the posterior wal of the acetabulum, the stress of acetabulum areas and displacement of acetabular unit were calculated with finite element software Ansys 13.0 software under 300, 600, 900 and 1 200 N. RESULTS AND CONCLUSION:(1) A three-dimensional finite element model of the hip and the femur was successful y established, consisting of 284 183 nodes and 160 665 units. (2) The characteristics of the stress distribution of acetabulum region:the maximal stress was concentrated on the posterosuperior part of acetabular crest, fol owed by the posterior wal and the anterior wal in order in upright position under different loads. The stress transmitted by four ways:from acetabular crest to ilium, along linea terminalis of pelvis to sacroiliac joint, in the acetabular sockets, and along the pubic ramus. The stress and the propagation distance were increasing as the loads increased. Acetabular element stress variable was increased. (3) Above results indicated that three-dimensional finite element model of the human hip joint established by Mimics 14.0 based on CT data matches the anatomical structure in a great degree, could be used in the biomechanics analysis under different loads, and has a guiding significance for design of artificial hip prosthesis.

Diagnosis and prenatal diagnosis to a family of hemoglobin variant with α-thalassemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Diagnosis and prenatal diagnosis to a family of hemoglobin variant with α-thalassemia.</p><p><b>METHODS</b>Whole blood cell analysis, hemoglobin analysis by capillary zone electrophoresis (CZE), Gap-PCR, polymerase chain reaction-reverse dot blot (PCR-RDB) assay and DNA sequencing.</p><p><b>RESULTS</b>Hb Zurich Albisrieden with α°-thalassemia lead to severe anemia. The genotype of fetus is also Hb Zurich Albisrieden with α°-thalassemia.</p><p><b>CONCLUSION</b>Abnormal hemoglobin with α-thalassemia may lead to severe anemia, Prenatal diagnosis of thalassemia has the vital significance for eugenic birth.</p>

Development of a thalassemia gene diagnosis method for dried blood spots / 国际检验医学杂志

Objective To devolope a method for extracting DNA from dried blood spots (DBS)and optimizing the operating procedure,which could be applied to clinical gene diagnosis of thalassemia.And the cross contamination of DBS punching and the storage stability of DBS were studied.Methods A total of 1 50 blood specimens were collected,and DBS were prepared.Circles (3 mm in diameter)were punched in the DBS,and eluted with lysis buffer.The eluting method and operating procedure were opti-mized.Genomic DNA extracted from the elution solution by magnetic beads,and were performed thalassemia gene test.Finally jud-ging whether the results of DBS and whole blood were consistent.Two methods of thalassemia gene test were used in DBS and the compatibility of DBS processing method was verified.Judging whether there was cross contamination of DBS punching by the thalassemia gene test results of blank hole which were punched in the blank filter paper between thalassemia positive DBS.The DBS storage stability in thalassemia gene test was verified by detecting the DBS which were dry stored at room temperature for 6 and 9 months.Results 5 circles (3 mm in diameter)DBS were vibrating eluted at 55 ℃ for 1 hour,the DNA concentration extracted from the elution solution was 10-20 ng/μL,which was dissolved in 50 μL solution,and the DNA quality was good.The thalassemia gene test results of DBS and whole blood were the same,and the DBS results of two thalassemia gene test methods were the same too. The cross contamination of DBS punching was not detected in thalassemia gene test.The DBS which were dry stored at room tem-perature for 6 and 9 months could be stably performed thalassemia gene test.Conclusion DBS could be used to perform thalassemia gene test,which is accurate,convenient and stable.It is an ideal way for specimen referral of thalassemia gene test.

Comparison of three different α-thalassemia prenatal screening strategies used in Guangdong, China / 中华围产医学杂志

Objective To compare the effect and cost of three different α-thalassemia prenatal screening strategies used in Guangdong, China, and to provide evidence for α-thalassemia prevention. Methods In total, 13 284 hospital-delivery couples and 13 369 newborns/fetuses (offspring) from 21 counties or districts of Guangdong Province were included in this study, who were treated from June to December 2012. Mean cell volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin A2 (Hb A2) were detected in the couples, and 6 types ofα-globin gene mutations were found in all couples and newborns. The strategies were MCV/MCH and serum Hb A2 (protocolⅠ) or parallel screening based on pregnant women (protocolⅡ), and serum screening based on couples (protocolⅢ). The validity and reliability of the three strategies were then compared using the Chi-square test. Results The sensitivity and the specificity of pregnant women who wereα-thalassemia carriers in protocolⅠwere 74.82%(1 352/1 807) and 74.11%(8 506/11 477), and were 89.82%(1 623/1 807) and 48.60%(5 578/11 477) in protocol Ⅱ , respectively. And 1.67% (221/13 284) couples were bothα-thalassemia carriers by the gene test. The rate of missed diagnosis in bothα-thalassemia carrier couples in protocolsⅠ,ⅡandⅢwas 50.68%(112/221), 11.76%(26/221) and 11.31%(25/221), respectively. In couples who needed prenatal diagnosis, the rates of missed diagnosis, sensitivity, specificity, positive predictive value, and negative predictive value were 17.46%(11/63), 82.54%(52/63),98.35%(13 003/13 221), 19.26%(52/270) and 99.92%(13 003/13 014) in protocolⅠ;4.76%(3/63), 95.24%(60/63), 88.18%(11 658/13 221), 3.70%(60/1 623) and 99.97%(11 658/11 661) in protocolⅡ;and 3.17%(2/63), 96.83%(61/63), 59.31%(7 842/13 221), 1.12%(61/5 440) and 99.97%(7 842/7 844) in protocol Ⅲ , respectively. The diagnosis of severeα-thalassemia was not missed in all three screening strategies. The mean cost of protocols Ⅰ, Ⅱ and Ⅲ for detecting a couple who needed prenatal diagnosis was 37 049.23, 50 836.00 and 40 321.64 RMB, respectively. Conclusions The three screening protocols have good efficiency in screening forα-thalassemia. However, protocolsⅡandⅢare preferred when financial conditions permit.

Comparison of the effect of three β-thalassemia prenatal screening strategies using in Guangdong province / 中华妇产科杂志

Objective To compare the effect of three β-thalassemia prenatal screening strategies in Guangdong province. Methods A total of 13 284 hospital-delivered couples and 13 369 newborns were recruited from 91 hospitals in 21 counties or districts of Guangdong province from June to December 2012. Mean cell volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin A2 (Hb A2) were tested for all the couples, and all the couples and newborns were detected by 17 types ofβ-globin gene mutations. The effect of three β-thalassemia prenatal screening strategies were compared as following:(1) MCV/MCH with Hb A2 serial screening(SS):Hb A2 was tested if the woman′s MCV3.5, it meant positive. And if the woman wasβ-thalassemia carrier and her husband′s Hb A2>3.5, it meant couple positive. (2) MCV/MCH with Hb A2 parallel screening(PS):if the woman′s MCV3.5 pg, it meant couple positive. And the husband would be tested forβ-globin gene mutations if the woman was β-thalassemia carrier. (3) MCV/MCH with Hb A2 serial screening for couples(SSC):if one of the couple or both of them had MCV3.5, it meant couple positive. Results (1) For the SS strategy, the sensitivity was 92.69%(583/629);the specificity was 99.87%(12 638/12 655); the positive predictive value was 97.17%(583/600);and the negative predictive value was 99.64%(12 638/12 684). The results ofβ-globin gene mutations tested showed that the rate ofβ-thalassemia carriers was 4.74%(629/13 284) in the 13 284 pregnant women, and it was 4.29%(570/13 284) in their husbands. (2) The SS strategy detected 27 (0.20%,27/13 284) β-thalassemia carrier couples. For the SS strategy detecting β-thalassemia carrier couples, the missed diagnosis rate was 11.11%(3/27);the sensitivity was 88.89%(24/27);the specificity was 100.00%(27/27); the positive predictive value was 100.00%(24/24); and the negative predictive value was 99.98%(13 257/13 260). (3) When using the SS strategy for 13 369 offsprings, there were 582β-thalassemia carriers (4.35%,582/13 369), including 578 (99.31%,578/582) minorβ-thalassemia, 3 (0.52%,3/582) intermediaβ-thalassemia and 1 (0.17%,1/582) major β-thalassemia. The SS strategy detected 25 fetuses who neededβ-thalassemia prenatal diagnosis. (4) For the PS strategy, the sensitivity was 98.09%(617/629); the specificity was 88.73%(11 229/12 655); the positive predictive value was 30.20%(617/2 043); and the negative predictive value was 99.89%(11 229/11 241). (5) When using the PS strategy for theβ-thalassemia carrier couples, the sensitivity was 100.00%(27/27);the specificity was 95.55%(12 667/13 257);the positive predictive value was 4.38%(27/617);and the negative predictive value was 100.0%(12 667/12 667). (6) The PS strategy detected 28 fetuses who needed β-thalassemia prenatal diagnosis in 13 369 offsprings. (7) For the SSC strategy, the sensitivity was 93.80%(590/629); the specificity was 95.75%(12 117/12 655); the positive predictive value was 52.30%(590/1 128); and the negative predictive value was 99.68%(12 117/12 156). When the SSC strategy was used for the husbands, the sensitivity was 92.28%(526/570); the specificity was 95.27%(12 112/12 714);the positive predictive value was 46.63%(526/1 128); and the negative predictive value was 99.64%(12 112/12 156). (8) When the SSC strategy was used inβ-thalassemia carrier couples, the sensitivity was 100.00%(27/27);the specificity was 91.69%(12 156/13 257);the positive predictive value was 2.39%(27/1 128);and the negative predictive value was 100.00%(12 156/12 156). (9) The SSC strategy detected 28 fetuses who neededβ-thalassemia prenatal diagnosis. Conclusions All the three β-thalassemia prenatal screening strategies had good effect in clinical practice and public health. While in the high-prone area of β-thalassemia, MCV/MCH with Hb A2 parallel screening and MCV/MCH with Hb A2 serial screening for couples stratigies were better.

Analysis of economic burden of major and intermedia thalassaemia in Guangdong Province / 医学研究生学报

Objective There is a high occurrence rate of thalassaemia in Guangdong Province .Major and intermedia thalas-saemia bring severe burden for patients , families, and societies.This study aimed to reveal the economic burden of thalassaemia major and intermedia thalassaemia in Guangdong Province . Methods Eight areas of Guangdong Province were selected as the sampling ar-eas.Patients with major or intermedia thalassaemia were enrolled in the study .The patients′economic burden of this disease , inclu-ding direct economic burden , indirect economic burden and intangible economic burden was calcultated .The direct economic burden was estimated by outpatient fee , hospitalization expense , nutrition and transportation fees , indirect economic burden was evaluated u-sing disability adjusted life years ( DALY) combined with human capital , and intangible economic burden was calculated using method of willingness. Results Per average annual direct economic burden of 45 patients with major or intermedia thalassaemia was 43 058.66 yuan, per average annual indirect economic burden was 20 474.51 yuan, and per person intangible economic burden was 302 466.67 yuan. Conclusion Economic burden of major and intermedia thalassaemia is huge and most patients do not receive standardized treatment .More effective way should be taken to reduce the economic burden of thalassaemia and help the patients to re -ceive standardized treatment .

Gene diagnosis for a child with tuberous sclerosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the pathogenic mutation in a family affected with tuberous sclerosis.</p><p><b>METHODS</b>For the proband and its parents, mutational hotspots in the 11 exons of TSC1 and TSC2 gene were analyzed with DNA sequencing and bioinformatics tools.</p><p><b>RESULTS</b>A heterozygous c.4493G>C missense mutation was identified in the proband. The same mutation was however not found in the parents.</p><p><b>CONCLUSION</b>The missense mutation c.4493G>C probably underlie the tuberous sclerosis complex seen in the child.</p>

Establishment of a fluorescent polymerase chain reaction method for the detection of the SARS-associated coronavirus and its clinical application / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To establish a fluorescent polymerase chain reaction (F-PCR) method for detecting the coronavirus related to severe acute respiratory syndrome (SARS) and to evaluate its value for clinical application.</p><p><b>METHODS</b>The primers and the fluorescence-labeled probe were designed and synthesized according to the published sequence of the SARS-associated coronavirus genes. A F-PCR diagnosis kit for detecting the coronavirus was developed, and 115 clinical nasopharyngeal gargling liquid samples were tested.</p><p><b>RESULTS</b>The sequence of PCR amplified products completely matched the related sequence of the SARS-associated coronavirus genome. Forty-nine out of 67 samples from identified SARS patients and 8 of 18 samples from persons having close contact with SARS patients showed positive results. All 30 samples from healthy controls were negative.</p><p><b>CONCLUSION</b>The F-PCR method established may be a rapid, accurate and efficient way for screening and for the early diagnosis of SARS patients.</p>