Molecular diagnosis of a novel heterozygous 268C→T (R90C) mutation in TGIF gene in a fetus with holoprosencephaly and premaxillary agenesis

We report the sonographic diagnosis and molecular analysis of holoprosencephaly (HPE) and premaxillary agenesis in a second-trimester fetus with a 46,XY karyotype. Mutational sequence analyses for the entire coding region and exon–intron boundaries of SHH, ZIC2, SIX3 and TGIF genes identified a novel heterozygous missense TGIF mutation 268C→T (CGC→TGC change) that predicts an Arg90Cys substitution in the homeodomain region of TGIF. The proband's parents did not carry the mutation. The present case is an example of the heterogeneous entity of the HPE spectrum and demonstrates that adjunctive molecular analyses of distinct human genes for HPE can reassure genetic counselling by elucidating the genetic pathogenesis, especially in cytogenetically normal fetuses affected with HPE. Copyright © 2002 John Wiley & Sons, Ltd.     

Semilobar holoprosencephaly prenatal diagnosis: an unexpected complex rearrangement in a de novo apparently balanced reciprocal translocation on karyotype

We report a semilobar holoprosencephaly (HPE) in a post-intracytoplasmic-sperm-injection pregnancy. It was suggested by ultrasonography (US), documented on karyotype, identified with magnetic resonance imaging (MRI), established after birth and confirmed on post-mortem autopsy. An amniocentesis revealed a de novo apparently balanced reciprocal translocation 46,XY, t(7;8) (q31.3;q12). Fluorescence in situ hybridization (FISH) identified a deletion in the region of the Sonic Hedgehog gene (SHH) on der(8); nevertheless, the subtelomeric regions for chromosomes 7 and 8 were present. The parents decided to continue the pregnancy; a boy was born and survived for 3 days. The brain autopsy confirmed the semilobar HPE previously noted on US and MRI. Further, band-specific FISH revealed, in addition to SHH deletion, the presence of an inversion in the 7q translocated material on der(8). The parents' karyotypes were normal. An unexpected complex rearrangement was present in a de novo apparently balanced reciprocal translocation in a semilobar HPE. Copyright © 2007 John Wiley & Sons, Ltd.     

Prenatal diagnosis of trisomy 4p: a new locus for holoprosencephaly?

Trisomy of the short arm of chromosome 4 is a well-known syndrome, and several observations have been made in the last 30 years. Herein, we report a new observation of trisomy 4p in a fetus with a semi-lobar holoprosencephaly (HPE), dysmorphic features and multiple malformations. The diagnosis of HPE was made, at 33 weeks' gestation, on the fetus of a healthy G1P0 woman. Amniocentesis was performed for chromosome analysis and additional material was found on a chromosome 22. The couple elected to terminate the pregnancy and fetal examination was realized. Conventional and molecular cytogenetic studies were performed on the fetus and the parents, which showed that the additional material found on one chromosome 22 corresponded to the short arm of chromosome 4 and therefore led us to establish a diagnosis of trisomy 4p inherited from the malsegregation of a paternal translocation t(4;22)(q12;q11.1). The etiology of HPE is very heterogeneous; it includes non-genetic factors such as maternal diabetes and genetic causes. HPE cases have been described in association with many chromosomal anomalies, trisomy 13 being the most frequent. However, to our knowledge, HPE has never been previously reported in association with a trisomy involving solely the short arm of chromosome 4. Copyright © 2005 John Wiley & Sons, Ltd.     

Prenatal diagnosis of partial monosomy 18p(18p11.2→pter) and trisomy 21q(21q22.3→qter) with alobar holoprosencephaly and premaxillary agenesis

A prenatal diagnosis of partial monosomy 18p(18p11.2→pter) and trisomy 21q(21q22.3→qter) in a fetus with alobar holoprosencephaly (HPE) and premaxillary agenesis (PMA) but without the classical Down syndrome phenotype is reported. A 27-year-old primigravida woman was referred for genetic counselling at 21 weeks' gestation due to sonographic findings of craniofacial abnormalities. Level II ultrasonograms manifested alobar HPE and median orofacial cleft. Cytogenetic analysis and fluorescence in situ hybridization (FISH) on cells obtained from amniocentesis revealed partial monosomy 18p and a cryptic duplication of 21q,46,XY,der(18)t(18;21)(p11.2;q22.3), resulting from a maternal t(18;21) reciprocal translocation. The breakpoints were ascertained by molecular genetic analysis. The pregnancy was terminated. Autopsy showed alobar HPE with PMA, pituitary dysplasia, clinodactyly and classical 18p deletion phenotype but without the presence of major typical phenotypic features of Down syndrome. The phenotype of this antenatally diagnosed case is compared with those observed in six previously reported cases with monosomy 18p due to 18;21 translocation. The present study is the first report of concomitant deletion of HPE critical region of chromosome 18p11.3 and cryptic duplication of a small segment of distal chromosome 21q22.3 outside Down syndrome critical region. The present study shows that cytogenetic analyses are important in detecting chromosomal aberrations in pregnancies with prenatally detected craniofacial abnormalities, and adjunctive molecular investigations are useful in elucidating the genetic pathogenesis of dysmorphism. Copyright © 2001 John Wiley & Sons, Ltd.     

Intensified wintertime secondary inorganic aerosol formation during heavy haze pollution episodes (HPEs) in Beijing, China

Air pollution in China is complex, and the formation mechanism of chemical components in particulate matter is still unclear. This study selected three consecutive heavy haze pollution episodes (HPEs) during winter in Beijing for continuous field observation, including an episode with heavy air pollution under red alert. Clean days during the observation period were selected for comparison. The HPE characteristics of Beijing in winter were: under the influence of adverse meteorological conditions such as high relative humidity, temperature inversion and low wind speed; and strengthening of secondary transformation reactions, which further intensified the accumulation of secondary aerosols and other pollutants, promoting the explosive growth of PM_2.5. PM_2.5/CO values, as indicators of the contribution of secondary transformation in PM_2.5, were approximately 2 times higher in the HPEs than the average PM_2.5/CO during the clean period. The secondary inorganic aerosols (sulfate nitrate and ammonium salt) were significantly enhanced during the HPEs, and the conversion coefficients were remarkably improved. In addition, it is interesting to observe that the production of sulfate tended to exceed that of nitrate in the late stage of all three HPEs. The existence of aqueous phase reactions led to the explosive growth sulfur oxidation ratio (SOR) and rapid generation of sulfate under high relative humidity (RH>70%).     

The solitary median maxillary central incisor (SMMCI) syndrome: Associations,prenatal diagnosis,and outcomes

Solitary median maxillary central incisor (SMMCI) syndrome is a complex disorder consisting of multiple, developmental defects involving midline structures of the head, which includes the cranial bones, the maxilla, and its container dentition (specifically the central incisor tooth germ), together with other midline structures of the body. SMMCI may appear as an isolated trait or in association with other midline developmental anomalies. We describe the case of a patient with SMMCI. He presented with a solitary median maxillary incisor, short stature, corpus callosum anomalies and a microform of holoprosencephaly (HPE), diabetes insipidus, and neurodevelopmental delay. The diagnosis was performed postnatally based on clinical features, radiological imaging, and a comprehensive genetic study. SMMCI can be diagnosed during the prenatal or neonatal periods or during infancy. Evaluation of the superior maxillary bone is important for prenatal diagnosis. Direct evaluation through bidimensional ultrasound or the use of multiplanar ultrasound or tridimensional reconstruction should be performed in cases of brain or face malformations. Early diagnosis can contribute to improved prenatal assessment and postnatal management.     

石化企业员工心理健康状况调查分析

目的了解石化企业员工的心理健康状况,采取相应的心理健康干预措施,提高企业员工的心理健康水平。方法采用症状自评量表（SCL-90）,抽取1472名石化企业员工进行测试。人机对话,电脑评定。对结果进行了统计分析并与国内群体常模进行了比较。结果石化企业员工症状自评量袁评定心理健康状况好1048人,占71．20％;心理健康状况良好334人,占22．69％;心理健康状况一般90人,占6．11％。症状自评量表的各项因子均分与全国常模比较：阳性项目、躯体化和恐怖因子均分高于全国常模;强迫症状、人际关系和忧郁因子均分低于全国常模;焦虑、敌对、偏执和精神病性因子均分与全国常模无差异。     

Short communication kazal type trypsin inhibitor in amniotic fluid in fetal developmental disorders

The amniotic fluid concentrations of the Kazal type trypsin inhibitor were studied in pregnancies with fetal developmental disorders. The samples were obtained by amniocentesis between 14 and 19 weeks of gestation. In cases with fetal malformations, the level was below the normal 10th centile in 15 out of 28 cases (54 per cent, P<0.05) and above the normal 90th centile in 2 cases (7.1 per cent). Low values were common in cases with intrauterine fetal death or congenital nephrosis. The levels were normal in fetal chromosomal aberrations.     

控释氮肥减量配施对土壤氨挥发和N2 O排放的影响

施用控释氮肥是提高氮素利用效率、减少氮素损失的重要途径.为研究聚合物包膜氮肥与普通尿素配比减量施用对旱作棕壤氨挥发和N₂O排放的影响,利用15N同位素标记技术,通过5个不同氮肥施用量处理,分析施肥后土壤的氨挥发和N₂O排放规律以及玉米的当季氮肥利用率.结果表明:①土壤氨挥发主要出现在施肥后的前2周,普通尿素氨挥发速率最大可达4.04 kg/（hm2·d）,最大值出现在施肥后第7天,施用配比包膜氮肥氨挥发峰值出现时间比普通尿素延迟2 d,且氨挥发总量明显降低,为2.15 kg/（hm2·d）.②对于各处理下的氨挥发总量,无氮处理（CK）为3.69 kg/hm2,常规尿素处理（NU）为18.64 kg/hm2,配比控释氮肥处理（PU1）为9.39 kg/hm2,减量配比控释氮肥处理（PU2）为6.44 kg/hm2,再减量配比控释氮肥处理（PU3）为5.02 kg/hm2.③N₂O排放规律呈现先平稳后升高的趋势,较高的N₂O排放通量集中在施肥后的55~91 d之间.N₂O排放峰值最高的是常规尿素处理,在施肥后第79天出现,达到0.299 mg/（m2·h）,施用配比包膜氮肥N₂O排放峰值均低于常规尿素处理.④施用配比包膜氮肥玉米产量高于普通尿素处理,减量配比包膜氮肥不会降低玉米产量.⑤土壤氨挥发总量与施氮量呈显著正相关.施用配比包膜氮肥相比于普通尿素可显著减少土壤氨挥发,减量配施氮肥相比于全量施肥可显著减少土壤氨挥发.因此,施用配比包膜氮肥,可在保证粮食产量的前提下减少氮肥投入,降低氮肥的气态损失,从而降低环境风险.      

First-trimester maternal serum alpha-fetoprotein as a marker for fetal chromosomal disorders

We evaluated first-trimester maternal serum alpha-fetoprotein (MS-AFP) as a marker for fetal chromosomal disorders. The multicentre study was performed under the auspices of the Dutch Working Party on Prenatal Diagnosis. MS-AFP was measured in 2404 normal pregnancies and 72 chromosomally abnormal pregnancies. The median multiple of the normal median (MOM) in 32 Down's syndrome pregnancies was 0·83 with a 95 per cent confidence interval ranging from 0·60 to 1·04. The difference between the distributions of first-trimester MS-AFP in normal and Down's syndrome pregnancies was statistically significant (t-test: t = 2·34, P<0·05). Thirty-one per cent of the Down's syndrome pregnancies were found below the tenth percentile. We found no difference between normal pregnancies and pregnancies with other chromosomal disorders (eight cases with trisomy 18, MOM = 1·26; seven cases with sex chromosome abnormalities, MOM = 1·07; 22 cases with a chromosomal mosaic pattern in chorionic villi, MOM = 1·08). We conclude that first-trimester MS-AFP can discriminate between normal and Down's syndrome pregnancies, but is not an effective marker. First-trimester MS-AFP has no value as a marker for other fetal chromosomal disorders.     

Fetal ear measurements in the prenatal detection of trisomy 21

Although prominent fetal nuchal folds, short long bones, echogenic bowel, and renal pelviectasis have been shown to be associated with trisomy 21, none has acceptable diagnostic efficacy. Diminished fetal ear lengths measured by ultrasound have recently been reported as yet another potential morphological marker for the prenatal detection of trisomy 21. To investigate this further, we measured ear lengths and widths of normal (n = 107) and trisomy 21 (n = 25) second-trimester formalin-preserved fetuses. The normal ear growth characteristics are described and compared with those of trisomy 21 fetuses. The normal fetal ear shape, not unlike that of the neonates, manifested a marked variation. When the ear lengths and widths were regressed against gestational age, the slopes of the regression lines for the two groups were found to be different (P < 0·001). However, despite the statistically significant difference between the ear sizes of normal and trisomy 21 fetuses, the wide range of normal variation seen at each gestational age means that the fetal ear measurements are not diagnostically helpful.     

Amniotic fluid fibrinolytic system in fetal neural tube defects

Second trimester amniotic fluid fibrinolytic system was examined in normal pregnancies and those complicated by anencephaly, spina bifida and fetal chromosome abnormalities. No significant difference was demonstrated between the fibrinolytic systems from normal pregnancies and those complicated by fetal chromosome abnormalities. In pregnancies complicated with anencephaly and spina bifida no significant difference was demonstrated for alpha-1-antitrypsin, alpha-1-antichymotrypsin and urokinase. Plasminogen was significantly lower (p < 0.02) and plasmin significantly higher (p < 0.001) than levels from normal amniotic fluid. Alpha-2-macroglobulin, fibrinogen, FDP-D and FDP-E were detected only in pregnancies complicated with anencephaly and spina bifida.     

Second-trimester maternal serum immunoreactive inhibin as a marker for fetal Down's syndrome

We measured immunoreactive inhibin in the maternal serum of 80 pregnancies with a chromosomally normal fetus and ten Down's syndrome pregnancies in the second trimester. The inhibin level in all Down's syndrome pregnancies was above the normal median; the multiple of the normal median (MoM) was 1.9. We found a statistically significant difference between the levels of inhibin in unaffected and affected pregnancies (Kolmogorov–Smirnov test: p <0.002). Using an arbitrarily chosen cut-off of 2.4 MoM, 40 per cent of Down's syndrome and 5 per cent of the normal pregnancies were found. We conclude that immunoreactive inhibin may be useful as a marker for fetal Down's syndrome.     

Prenatal diagnosis of congenital enzymopenic methaemoglobinaemia with mental retardation due to generalized cytochrome b5 reductase deficiency: First report of two cases

Prenatal diagnosis of congenital enzymopenic methaemoglobinaemia (CEM) with mental retardation was performed in two fetuses at risk for generalized NADH-cytochrome b₅ reductase deficiency. In the first case the enzyme activity of cultured amniotic cells was in the heterozygous to normal range. The mother delivered a normal baby with normal enzyme activity in cord blood cells. In the second case, the amniotic cells were almost completely enzyme deficient. The pregnancy was terminated, and the diagnosis of homozygous NADH-cytochrome b₅ reductase deficiency was confirmed in cord blood cells, in several different tissues and in cultured fibroblasts from the aborted fetus.     

Relative risk of abnormal karyotype in fetuses found to have an atrioventricular septal defect (AVSD) on fetal echocardiography

One hundred and twenty-five fetuses were identified as having an AVSD with normal venous connections, normal arterial connections and normal cardiac situs on fetal echocardiography. Fetal karyotype was known in 111 of these cases. The relative risk of fetal trisomy 21 at mid-trimester was 107 (95% CI 87–127) times the expected number of cases compared with risk from maternal age alone, and that for trisomy 21,18 or 13 was 95 (95% CI 79–109). This data may be useful in counselling pregnant women about risk of fetal karyotypic abnormality after a diagnosis of fetal AVSD. Copyright © 2005 John Wiley & Sons, Ltd.     

Cardiac blood flow studies in fetuses with haemoglobin bart's disease

Blood flow across the atrioventricular valves and outflow tracts was measured in 55 normal fetuses and 32 fetuses with haemoglobin (Hb) Bart's disease between 18 and 26 weeks of gestation. The mean velocities remained unchanged in both normal and affected fetuses over the gestations studied. The volume flow across both atrioventricular valves and outflow tracts increased as the gestation advanced in both normal and affected fetuses, but was significantly higher in affected than in normal fetuses. The same magnitude of increased flow was found in both hydropic and non-hydropic fetuses with Hb Bart's disease. These findings suggest that fetuses with severe and long-standing anaemia have a remarkable cardiac compensatory mechanism for the maintenance of tissue oxygenation. In response to anaemia and circulatory loading, the cardiac chambers and outflow tracts enlarge proportionately up to twice the normal values. Because of this response and the operation of the Frank-Starling mechanism, the heart is able to maintain a normal mean velocity of propulsion and the net output is increased to two to three times that in normal fetuses. Hydropic changes in these anaemic fetuses appear unrelated to cardiac failure as cardiac failure is not observed at the time that hydropic changes develop.     

First-trimester maternal serum human chorionic gonadotrophin as a marker for fetal chromosomal disorders

The Dutch Working Party on Prenatal Diagnosis has initiated a study on the possibilities of first-trimester screening for fetal chromosomal disorders. We report on maternal serum human chorionic gonadotrophin (MS-hCG) measurements in 1348 pregnancies with a chromosomally normal fetus and 53 pregnancies with a chromosomally abnormal fetus. The median MS-hCG concentration in 24 pregnancies with Down's syndrome was 1.19 multiples of the normal median (MoM). The MS-hCG distributions in normal and Down's syndrome pregnancies did not differ significantly (t-test: t = 1.945, p >0.05). We also found no difference between normal pregnancies and pregnancies with other chromosomal disorders (six cases of trisomy 18, MoM = 0.80; four cases of sex chromosome abnormality, MoM = 1.01; 17 cases of chromosomal mosaicism in chorionic villi, MoM = 1.11). Selecting an upper limit at the 90th centile could detect 25 per cent of pregnancies with Down's syndrome. We conclude that, in the first trimester, MS-hCG as a screening factor for Down's syndrome is of minor value. However, MS-hCG could be a useful factor in a first-trimester screening programme based on a combination of markers.     

Trisomic pregnancies have normal human chorionic gonadotropin bioactivity

Sera from women carrying either chromosomally normal or aneuploid fetuses in the first half of pregnancy were assayed for human chorionic gonadotropin (hCG) bioactivity in order to determine whether differences might provide the basis for a useful antenatal screen for aneuploidy. A mouse uterine weight assay was used to assess hCG bioactivity in sera from 35 patients undergoing chorionic villus sampling (12 normal pregnancies and 23 trisomic pregnancies) and in sera from 18 patients undergoing elective second-trimester abortion (12 presumed normal pregnancies, 3 trisomic pregnancies, and 3 pregnancies with neural tube defects). The hCG bioactivity to immunoactivity (B:I) ratio of normal pregnancies progressively decreased from 7.7±1.3 at 4–5 menstrual weeks, to 4.7±0.4 at 9–12 menstrual weeks, to 3.3±0.5 at 16–20 menstrual weeks. There were no significant differences in the B:I ratios between normal and aneuploid pregnancies in either the first-trimester (4.7±0.4 versus 5.2±0.3) or the second-trimester samples (3.3±0.5 versus 2.6±0.3), despite significantly greater hCG concentrations in the trisomic pregnancies. We conclude that while aneuploid pregnancies display dysfunctional regulation of hCG expression, the bioactivity of their hCG is normal and does not appear to form the basis for a useful screen for aneuploidy.     

兰州市低碳数正构烷烃组分特征及大气化学反应活性分析

为明确兰州市大气环境常态下低碳数正构烷烃（C₅~C₁₉）质量浓度变化、组分特征及大气化学反应活性之间的关系,于2017年11月-2018年6月选取兰州市5个采样点,利用TENAX吸附管采集空气样品,应用TD-GC/MS（热脱附-气质联用）法对样品进行分析.对空气样品中低碳数正构烷烃大气化学反应活性的OFP（臭氧生成潜势）、·OH消耗速率、SOA（二次有机气溶胶）生成潜势进行评估计算,通过相关性分析及因子分析法分析低碳数正构烷烃的大气化学反应活性贡献率特征.结果表明:①在10种低碳数正构烷烃中,正己烷（C₆）对OFP的贡献率最大,正辛烷（C₈）对·OH消耗速率的贡献率最大,二者的贡献率分别为37.71%和37.64%.②在10种低碳数正构烷烃中正辛烷（C₈）对SOA生成潜势的贡献率最大,为50.02%.③大气化学反应活性参数相关性分析表明,低碳数正构烷烃总质量浓度与OFP、·OH消耗速率相关性显著（R分别为0.895和0.948）.④因子分析表明,5个未知因子所包含的化学反应活性信息量在94.511%以上,所含信息量也体现了未知因子组成的重要性,可为进一步解析大气化学反应活性提供参考.研究显示,正辛烷、正己烷是低碳数正构烷烃的2个关键活性组分,正辛烷是大气化学反应活性贡献率最大的化合物之一,也是汽车尾气排放源的主要组成部分,正己烷是人为源与自然源的混合产物.      

气象条件对上甸子地区气溶胶散射特征的影响

利用北京地区上甸子站气溶胶散射系数、PM2.5质量浓度和气象要素1 a的观测资料,研究不同天气条件下上甸子地区散射系数的变化特征,并讨论了气象条件对散射系数的影响.结果表明,散射系数在雾霾天最高608.4 Mm-1,其次为雾天500.6 Mm-1和霾天423.7 Mm-1,是一般天气散射系数的6.4～9.2倍.在各类天...