Peri- and paracentric inversions in chromosome 12: Prenatal diagnosis and family study

Three different types of chromosome 12 inversion were seen in 15 individuals out of 44 individuals examined in one 8 generation family. Type 1: a pericentric inversion inv(12) (p112; q131) was found in 7 individuals and twice at prenatal diagnosis. Type 2: a paracentric inversion inv(12) (p123; p131) was seen in two individuals. Two individuals carried both inversion chromosomes, namely type 1 and type 2. The two inversion chromosomes were transmitted from each of the parents. Type 3: a double pericentric and paracentric inversion (type 3) inv(12) (p123; p131) (p112; q131) was observed in the daughter of one of the carriers of type 1 and 2 inversions and again at prenatal diagnosis in her son. The double inversion most likely arose through crossing-over in between the two inversion loops. A balanced translocation t(7; 13) and the inversion type 1 was observed in one individual, who transmitted the translocation only to an offspring. The frequency of inversions in amniotic fluid cells observed in our laboratory was 1·9 per cent. The clinical implications of these findings are discussed.     

Prenatal diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency by steroid analysis in the amniotic fluid of mid-pregnancy: Comparison with HLA typing in 17 pregnancies at risk for CAH

Amniotic fluid (AF) levels of 17-hydroxyprogesterone (17OHP) and testosterone (T) were determined at 16–17 weeks in 17 pregnancies at risk for CAH and results compared to 75 normal controls. The fetus was predicted to be unaffected in 12 cases on the findings of normal AF levels of both 17OHP and T and the latter allowed a correct prediction of fetal sex in all instances. HLA typing confirmed normality in 12 cases revealing 5 carriers, 5 homozygous normal and 2 indeterminate. Steroid levels of the 2 groups were similar. Three fetuses were predicted to be CAH affected on unambiguously high levels of 17OHP and T (in female only). HLA typing was in agreement, and the diagnosis was confirmed in 2 abortuses and a female newborn by physical and hormonal studies. In the last 2 cases AF levels of OHP and T were normal but HLA (A/B/C) genotypes were identical to the CAH affected siblings. Normal physical and hormonal findings in the 2 aborted fetuses would exclude the possibility of an in utero virilizing form of CAH. The discrepancy could be explained on the basis that the fetuses had an allelic form of 21-hydroxylase deficiency or on the basis of recombination (not fully tested). It is concluded that a fully informative prenatal diagnosis of CAH should not rely entirely on HLA typing but on hormonal studies.     

Erythroid-specific antibodies enhance detection of fetal nucleated erythrocytes in maternal blood

Fetal nucleated erythrocytes (NRBC) in maternal blood are a non-invasive source of fetal DNA for prenatal genetic screening. We compared the effectiveness of three monoclonal antibodies for the separation of fetal cells from maternal blood by flow sorting. Mononuclear blood cells from 49 healthy pregnant women were incubated with antibody to CD 71, CD 36, and/or glycophorin A (GPA), employed singly or in combination with each other. These monoclonal antibodies recognize surface antigens on haematopoietic precursor cells. Successful isolation of fetal cells was defined as detection of Y chromosomal sequences in maternal blood from women carrying male fetuses, with absence of Y sequences when female fetuses were carried. Thus, gender prediction accuracy was used as a measure of fetal cell separation. Using anti-CD 71 to isolate fetal cells, gender prediction was 57 per cent correct; with anti-CD 36, it was 88 per cent correct. Anti-GPA, an erythrocyte-specific antigen, used alone or in combination with anti-CD 71 or 36, improved gender prediction to 100 per cent. We conclude that antibody to GPA improves the retrieval of fetal NRBC from maternal blood, permitting genetic analysis by the polymerase chain reaction.     

Prenatal diagnosis of gastrointestinal obstruction: A correlation between prenatal ultrasonic findings and postnatal operative findings

The impact of prenatal sonographic diagnosis of oesophageal and gastrointestinal obstructions has been analysed over a 10-year period. Three groups of patients were evaluated. The first group consisted of 46 newborns with abnormal prenatal sonogratns, 41 of which were confirmed to have intestinal obstruction postnatally. The second group consisted of 17 neonates with normal prenatal sonograms who had intestinal obstruction postnatally. The third group included 56 newborns who did not undergo a prenatal sonogram but who had intestinal obstruction confirmed at surgery. Polyhydramnios without the appearance of a stomach on ultrasound was diagnostic of pure oesophageal atresia. Polyhydramnios with intestinal dilation was diagnostic of intestinal obstruction. Although surgery was performed earlier in the infants diagnosed prenatally with ultrasound, mortality was no less than in the group that did not undergo a prenatal sonogram, probably because of the high incidence of associated anomalies.     

陆地生态系统的恢复--模拟全球变化所引起的酸性输入减少和海盐输入增加的影响

到2010年<哥德堡议定书>正式实施时,欧洲自20世纪70年代末以来已减少的酸化硫和氮释放量将进一步减少.这里我们论述了通过使用应用于3个大型"清洁雨"实验(即分别在挪威里斯达尔谢伊阿[Risdalsheia],瑞典耶德松[Gardsjon]以及丹麦克洛斯特海泽[Klosterhede]的所谓"屋顶实验")的酸化模型MAGIC讨论恢复酸化陆地生态系统的结果.<哥德堡议定书>的实施将启动通过重建盐基饱和恢复上述3处土壤的进程.恢复率较低,在今后30年中,盐基饱和增加不足5%.气候引发的风暴严重性的加剧将增加海盐输入生态系统的量.这将为土壤提供额外的碱阳离子,并使恢复速度翻一番,同时还将随着沉积的碱阳离子与存储在土壤中的酸性交换导致高海盐输入之后的强酸性脉动.因此,酸化集水区土壤和径流的进一步恢复将取决于酸沉积下降的数量和速率,在近岸系统的情况下,还取决于海盐输入事件的频率和强度.     

Amniotic fluid alpha-fetoprotein levels and prenatal diagnosis of autosomal trisomies

Pregnancies with fetal trisomy 21 have been associated with low amniotic fluid alpha-fetoprotein levels (AFAFP). This observation led to the suggestion that low AFAFP levels be used as a criterion for completion of a chromosomal analysis in patients who are not otherwise at increased risk for a fetal chromosome abnormality and in whom karyotyping might not have been completed for economic reasons. In order to assess the usefulness of such criteria, we reviewed the AFAFP levels of 90 cases of fetal trisomy 21, 23 cases of trisomy 18, and 10 cases of trisomy 13. These were compared with 2400 control samples with normal chromosome constitution. AFAFP levels were generally lower in pregnancies with trisomy 21, showing a median value of 0·72 MoM. However, 40 per cent of the trisomy 21 samples had AFAFP values greater than 0·8 MoM and 20 per cent were over 1·0 MoM. These data imply that over 50 per cent of Down syndrome cases might have been missed using a cut-off level of 0·70 MoM for completion of chromosome analysis. Using a higher cut-off level will leave only a small percentage of samples unkaryotyped. The distribution of AFP levels in trisomy 13 and 18 is no different from controls; we therefore believe that fetal karyotyping should be completed in every amniotic fluid sample obtained.