Experiences with unexpected structural chromosome aberrations in prenatal diagnosis in a danish series

The investigation of 5547 prenatal diagnoses showed 31 unexpected structural chromosome rearrangements. These included 3 Robertsonian translocations, 14 reciprocal translocations and 14 inversions. A11 were balanced, including 5 de novo rearrangements. In 3 of these cases an induced abortion was performed and in 2 cases children without detectable malformations were delivered.     

Uniparental disomy in fetuses diagnosed with balanced Robertsonian translocations: risk estimate

Forty-two fetuses with non-homologous Robertsonian translocations were analyzed for uniparental disomy (UPD). One fetus with a de novo translocation t(13q;14q) had maternal isodisomy of chromosome 14. In a summary of the published data (including the present study), 315 cases were analyzed for UPD after prenatal diagnosis of balanced Robertsonian translocations, of these two fetuses had UPD, giving a risk estimate of 0.65% (CI 0.2–2.3). This risk justifies the recommendation of UPD analysis in fetuses diagnosed prenatally with Robertsonian translocations, with the emphasis on the chromosomes known to contain imprinted genes, such as 14 and 15. We also discuss the possibility of UPD in offspring of Robertsonian translocation carriers with normal karyotype. Based on the risk for UPD in fetuses with Robertsonian translocation we suggest to test these fetuses for UPD and to do so on amniocytes rather than chorionic villi when the risk for unbalanced karyotype is ∼1%, comparable to the risk for UPD. Copyright © 2002 John Wiley & Sons, Ltd.     

Variation in the levels of pregnancy- specific β-1-glycoprotein in maternal serum from chromosomally abnormal pregnancies

Human pregnancy-specific β-1-glycoprotein (SP1) was assayed retrospectively in stored maternal serum (MS) samples from 82 chromosomally abnormal pregnancies and 377 matched controls. The median MSSP1 concentration in 48 Down's syndrome pregnancies was significantly elevated at 1.17 multiples of the control median (MOM), and significantly reduced (0.5 MOM) in a group of eight cases of unbalanced translocations. There was no significant difference in median SP1 concentrations in cases of trisomy 18, trisomy 13, balanced translocations, or sex chromosome abnormalities. A comparison with human chorionic gonadotrophin results in the same series of samples indicates that SP1 is a less sensitive predictor of Down's syndrome pregnancies.     

Prenatal diagnosis and postnatal follow-up of a child with two de novo unrelated balanced reciprocal translocations

Two unrelated, apparently balanced, reciprocal translocations involving chromosomes 3 and 17, and 10 and 15 were found in cultured amniotic fluid cells from a 41-year-old 10-gravida. Chromosome analysis of peripheral blood lymphocytes of both parents revealed normal katryotypes. Post-partum examination of lymphocyte cultures from the proband confirmed the chromosome rearrangements. The child showed normal development during follow-up examinations up to the age of 4 years.     

A case of mosaicism involving an unstable 13/14 Robertsonian translocation

Prenatal diagnosis of mosaicism involving an apparently unstable 13/14 Robertsonian trans-location is reported. This illustrates the difficulties encountered in counselling when mosaicism is ascertained prenatally. Other reported examples of apparently unstable Robertsonian translocations are discussed.     

First-trimester prenatal diagnosis of homozygous (14;21) translocation in a fetus with 44 chromosomes

A (14;21) homozygous Robertsonian translocation was detected by first-trimester prenatal diagnosis. The related parents were heterozygous for the same translocation. At birth the baby was physically normal and had a normal psychomotor development. Together with a few previous observations in living homozygotes for (13;14) translocations, this case corroborates the idea that these subjects with 44 chromosomes are healthy without dysmorphic features.     

Prenatal diagnosis of holoprosencephaly in two fetuses with der (7)t(1;7)(q32;q32)pat inherited from the father with double translocations

The presence of two independent translocations in one person is rare. Herein, we report the prenatal diagnosis of two sibling fetuses with holoprosencephaly, whose father is a carrier of double translocations. The karyotype of the father is 46,XY, t(1;7) (q32;q32), t(14,15) (q32.1;q26.3). The two fetuses had variable facial dysmorphisms and identical cytogenetic abnormality—a derivative (7) t(1;7) (q32;q32) inherited from the father. The proband 1 showed a small mouth, a single median eye and a proboscis above the eye, while the proband 2 showed hypotelorism, a flat nose, cleft lip and cleft palate. Both fetuses also had alobar holoprosencephaly. Haploinsufficiency of the sonic hedgehog gene at 7q36 does account for the occurrence of holoprosencephaly in the two fetuses with a deletion of distal 7q (7q32 → qter). Copyright © 2003 John Wiley & Sons, Ltd.     

Risk estimates for uniparental disomy following prenatal detection of a nonhomologous Robertsonian translocation

Carriers of nonhomologous Robertsonian translocations (ROB) are at risk for having offspring with uniparental disomy (UPD). Although risk estimates have been calculated in several independent studies, the estimates have not been optimal because most studies are not of sufficient size and UPD events are rare. However, these collective data have provided the opportunity to derive an overall risk estimate for UPD in the fetus after the prenatal identification of a ROB. Copyright © 2006 John Wiley & Sons, Ltd.     

Rapid interphase analysis for prenatal diagnosis of translocation carriers using subtelomeric probes

Interphase fluorescence in situ hybridization (FISH) has become an accepted laboratory technique for the rapid and preliminary prenatal assessment of chromosome aneuploidy. The introduction of subtelomeric FISH probes now allows for the molecular–cytogenetic analysis of terminal chromosome rearrangements. In a prospective study, we examined the prenatal use of subtelomeric probes on interphase cells to rapidly detect the carrier status of a fetus when a parent carried a known reciprocal or Robertsonian chromosome translocation. Three of the cases were identified as being abnormal. All cases were confirmed by routine cytogenetic analysis. These findings clearly demonstrated the utility of this technique and these probes to rapidly and correctly identify balanced and unbalanced chromosome anomalies of a fetus that could result from parental translocations. Copyright © 2002 John Wiley & Sons, Ltd.     

Uptake, translocation, and debromination of polybrominated diphenyl ethers in maize

Uptake, translocation and debromination of three polybrominated diphenyl ethers (PBDEs), BDE-28, -47 and -99, in maize were studied in a hydroponic experiment. Roots took up most of the PBDEs in the culture solutions and more highly brominated PBDEs had a stronger uptake capability. PBDEs were detected in the stems and leaves of maize after exposure but rarely detected in the blank control plants. Furthermore, PBDE concentrations decreased from roots to stems and then to leaves, and a very clear decreasing gradient was found in segments upwards along the stem. These altogether provide substantiating evidence for the acropetal translocation of PBDEs in maize. More highly brominated PBDEs were translocated with more difficulty. Radial translocation of PBDEs from nodes to sheath inside maize was also observed. Both acropetal and radial translocations were enhanced at higher transpiration rates, suggesting that PBDE transport was probably driven by the transpiration stream. Debromination of PBDEs occurred in all parts of the maize, and debromination patterns of different parent PBDEs and in different parts of a plant were similar but with some differences. This study for the first time provides direct evidence for the acropetal translocation of PBDEs within plants, elucidates the process of PBDE transport and clarifies the debromination products of PBDEs in maize.     

Prenatal diagnosis of a homologous Robertsonian translocation involving chromosome 15

We report the prenatal diagnosis of a fetus with a de novo Robertsonian translocation: 45,XY,der(15;15)(q10;q10). Although Robertsonian translocations are common chromosomal rearrangements, those involving homologous chromosomes are infrequent. Since chromosome 15 is imprinted, uniparental disomy (UPD) is a concern when chromosomal rearrangements involving chromosome 15 are identified. In the present case, UPD studies showed normal biparental inheritance. In contrast to the fact that most homologous acrocentric rearrangements are isochromosomes, these results indicate postzygotic formation of a Robertsonian translocation between biparentally inherited chromosomes 15. Copyright © 2001 John Wiley & Sons, Ltd.     

Nuchal translucency thickness and outcome in chromosome translocation diagnosed in the first trimester

In order to determine the significance of nuchal translucency thickness on the subsequent natural history of first-trimester fetuses with a chromosome translocation, seven consecutive cases diagnosed between 11 and 13 weeks of gestation were reviewed. Nuchal translucency measurements were successfully obtained before chorionic villus sampling (CVS) in all cases. Three fetuses had an unbalanced translocation and all were associated with increased nuchal translucency and multiple anomalies at the detailed second-trimester scan. There were no survivors in this group. The remaining four fetuses had a balanced translocation; all had normal nuchal translucency thickness and no structural anomalies were detected in the second trimester. Three of these fetuses were born at ≥35 weeks of gestation and were phenotypically normal. However, an unexpected single fetal demise occurred in a dichorionic twin pregnancy at 28 weeks of gestation. It is concluded that nuchal translucency measurements provide important prognostic information on pregnancy outcome in first-trimester fetuses with a chromosome translocation. In parents with a known balanced translocation, the detection of increased nuchal translucency at 11–14 weeks of gestation is associated with unbalanced translocations, structural anomalies and poor pregnancy outcome. Copyright © 2001 John Wiley & Sons, Ltd.     

Early amniocentesis at 11–14 weeks' gestation for the diagnosis of fetal chromosomal abnormality—a clinical evaluation

Early arnniocentesis between 11 and 14 weeks' gestation was offered to 110 women at risk of a chromosomally abnormal fetus due to maternal age. Four were found to be unsuitable for the procedure, and 106 early amniocenteses were performed. In 102 cases, clear amniotic fluid was obtained with a single tap. There were two dry taps and two bloodstained tapis; sampling was repeated in three of these cases before 15 weeks. In the fourth case, placental biopsy was performed at 16 weeks. Thus, we were able to obtain a satisfactory sample in all but three cases(2.8 percent). Karyotyping of cells harvested from the early amniotic fluid samples was successful in all the 105 cases. Cell culture from the initial samples revealed a normal karyotype in 99 cases, two balanced translocations, two tetraploid karyotypes, and two cases of pseudomosaicism. Of the 105 pregnancies successfully sampled, there have been two losses to date (1–8 per cent). Two further patients presented with premature rupture of membranes, both pregnancies having successful outcomes. Sixty-two babies have delivered to date, with four congenital anomalies. There were no respiratory problems. Twenty-nine pregnancies are continuing without known complications, and details are not yet available on the remaining 12. The results indicate that early arnniocentesis may replace the traditional test at 15–17 weeks.     

Prenatal screening for chromosome abnormalities using maternal serum chorionic gonadotrophin,alpha-fetoprotein,and age

Human chorionic gonadotrophin (hCG) levels were assayed retrospectively in stored maternal serum samples from 78 chromosomally abnormal pregnancies and 410 controls matched for gestation and maternal age. The median serum hCG concentration in 49 pregnancies with Down's syndrome was significantly elevated, at 2.18 multiples of the normal median. Significantly reduced hCG concentrations were found in a group of four trisomy 18 pregnancies (all less than 0.4 multiples of the median). Eight cases of unbalanced chromosome rearrangements appeared to show some lowering of hCG levels, while there was no significant difference in the levels in the cases of trisomy 13, balanced translocations, and sex chromosome abnormalities. Maternal serum hCG alone is a better indicator of Down's syndrome pregnancies than maternal age or maternal serum alpha-fetoprotein (AFP), either individually or in combination, and provides a further virtually independent measure of risk. On the basis of our findings, screening for Down's syndrome using hCG and AFP results combined with maternal age risks is predicted to result in a higher detection rate (57 per cent) for a lower false-positive rate (5.0 per cent) than would be attainable by combined AFP and age screening (37 per cent detection at a 6.6 per cent false-positive rate).     

Preimplantation genetic diagnosis using FISH for carriers of Robertsonian translocations: the Portuguese experience

Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis for couples at risk of transmitting genetic disorders to their offspring. We present a fluorescence in situ hybridization (FISH) analysis of embryos obtained after seven PGD cycles in six couples with Robertsonian translocations and male factor infertility: 4 der(13;14), 1 der(14;21) and 1 der(15;21). Of 74 metaphase II (MII) injected oocytes, 61 (82.4%) fertilized normally and cleaved. Of these, 37/61 (60.7%) embryos were of high morphological quality with ≥6 blastomeres. After biopsy of 44 embryos at day 3 of development, seven degenerated, seven arrested in development and 30/44 (68.2%) evolved, of which 25/30 (83.3%) reached the morula/blastocyst stage. Analysis of biopsied blastomeres showed 23/44 (52.3%) of normal/balanced embryos, of which 15 (11 at the morula/blastocyst stage) were transferred in six cycles. One term pregnancy was achieved, which ended by cesarean section at 37 weeks of gestation, giving birth to two healthy newborn. Analysis of 49 embryos (excluding 12 inconclusive cases) showed a predominance of alternate segregation (38/49, 77.6%) over adjacent segregation (7/49, 14.3%), with one (2%) being a polyploid mosaic and three (6.1%) chaotic. Copyright © 2002 John Wiley & Sons, Ltd.     

Preimplantation genetic diagnosis at 20 years

First reported in 1990, PGD has evolved into a complementary form of prenatal diagnosis offering novel indications. DNA for PGD can be recovered with equal safety and facility from polar bodies I and II, blastomere (8 cell embryo) and trophectoderm (5–6 day blastocyst). Diagnostic accuracy is very high (>99%) for both chromosomal abnormalities and single gene disorders. Traditional application of FISH with chromosome specific probes for detecting aneuploidy and translocations may be replaced or complemented by array comparative genome hybridization (array CGH); biopsied embryos can now be cryopreserved (vitrification) while analysis proceeds in orderly fashion. PGD has been accomplished for over 200 different single gene disorders. Novel indications for PGD not readily applicable by traditional prenatal genetic diagnosis include avoiding clinical pregnancy termination, performing preconceptional diagnosis (polar body I), obtaining prenatal diagnosis without disclosure of prenatal genotype (nondisclosure), diagnosing adult-onset disorders particularly cancer, and identifying HLA compatible embryos suitable for recovering umbilical cord blood stem cells. Copyright © 2010 John Wiley & Sons, Ltd.     

Trisomy 15 mosaicism owing to familial reciprocal translocation t(1;15): implication for prenatal diagnosis

We describe a 4-year-old female child with severe global mental retardation, myoclonic epilepsy, proximal hypotonia and dysmorphisms, whose prenatal diagnosis following amniocentesis revealed a constitutional female karyotype carrying a t(1;15)(q10;p11) familial reciprocal translocation. Post-natal high-resolution karyotype, Fluorescence in situ hybridization (FISH) screening for subtelomeric rearrangements, VNTR search for UPD15 in the blood and fibroblast, and WCP1 and 15 in the mother, failed to provide an explanation for the complex clinical phenotype of the proband. Since the pachytene configuration of the translocated chromosomes defines a high probability of 3:1 segregation, an extensive workup was undertaken to look for a possibly cryptic mosaicism. Four percent of the cells with trisomy 15 was found in the peripheral blood lymphocytes examined by classical cytogenetic technique and interphase FISH analysis. The clinical features associated with cryptic trisomy 15 mosaicism and the problems concerning prenatal diagnosis and genetic counselling for carriers of translocations at high risk of 3:1 segregation are discussed. Copyright © 2006 John Wiley & Sons, Ltd.     

硫酸亚铁和硝酸铁施用对根际土壤-水稻系统中镉运移的影响

我国稻田镉（Cd）污染治理刻不容缓.氮（N）、硫（S）和铁（Fe）的生物地球化学循环,以及Fe-N和Fe-S循环耦合体系,都与土壤-水稻系统中Cd运移密切相关.以N、S和Fe对水稻生长的营养供给为切入点,研发抑制稻米Cd累积的营养型阻控技术及产品,势必能为稻田Cd污染治理提供新的解决途径.本文在前期研究成果的基础上开展根际袋-盆栽试验,分析硫酸亚铁（FeSO₄）和硝酸铁［Fe（NO₃）₃］处理条件下根际土壤中Cd活性变化与水稻体内Cd转运规律,探索糙米Cd累积的影响因素及制约机制.结果表明,FeSO₄和Fe（NO₃）₃处理都显著减小了根际土壤中有效态Cd（NH₄Ac-Cd）含量,且前者减小的幅度（55.6%）小于后者（76.0%）;FeSO₄和Fe（NO₃）₃处理都明显改变了水稻体内Cd分布特征,但前者增大了糙米Cd含量（0.6mg ·kg^-1）,而后者却减小了糙米Cd含量（0.1mg ·kg^-1）.根表铁膜对Cd的吸附或与Cd共沉淀、水稻根、茎和叶对Cd的累积量增大以及根、茎和结节对Cd的转运能力增强,是导致FeSO₄处理中糙米Cd含量增大的重要原因;Fe（NO₃）₃处理中糙米Cd含量减小,则可归结为无定形铁矿物对Cd的吸附或与Cd共沉淀、铁硫化物与Cd共沉淀、茎和结节对Cd的累积量减小以及根、叶和结节对Cd的转运能力减弱.本研究成果将为后期营养型阻控产品及施用技术研发提供科学依据,并为我国稻田Cd污染治理提供重要参考.     

Pre- and perinatal findings in partial trisomy 7q resulting from balanced parental translocations t(7;21) and t(4;7)

We report on a fetus and a newborn, both with partial trisomy 7q21→qter due to different familial translocations, t(7;21)(q21.2;p12) and t(4;7)(q35;q21.2). Postmortem examination of the 19-week-old female fetus disclosed dysmorphic features, cleft palate, anomalies of the great vessels, intestinal malrotation and uterus bicornis. The newborn girl revealed a pattern of minor anomalies, cleft palate, cerebellar hypoplasia, and anomalies of pancreas, gall bladder and appendix. The clinical findings in three other reported fetuses with partial trisomy 7q described so far are reviewed. A duplication 7q21→qter, as found in the propositi, has only been described in 11 patients who all had a concurrent partial monosomy. Patient 1 is particularly interesting since she is, to our knowledge, the first reported case with pure trisomy 7q21/22→qter. We reviewed the phenotype of the previously described patients, compared it with the propositae, and summarized the clinical features of pure trisomy 7q21/22→qter. Copyright © 2001 John Wiley & Sons, Ltd.     

Preimplantation genetic diagnosis (PGD), a collaborative activity of clinical genetic departments and IVF centres

An Erratum has been published for this article in Prenatal Diagnosis 22 (5) 2002, 451. Preimplantation genetic diagnosis (PGD) requires the combined efforts of geneticists and workers in the field of reproductive medicine. This was studied on the basis of a questionnaire, sent to 35 members of the PGD Consortium of the European Society of Human Reproduction and Embryology (ESHRE). A reply was obtained from 20 centres. They represent the majority of activities in the field of PGD in the world. It is obvious that many of the activities (in vitro fertilisation, embryo culture and biopsy) take place in IVF units while others (counselling and diagnosis) are the responsibility of genetic diagnostic centres. The distances between both units vary considerably. In all but one centre sex determination is offered. Aneuploidy screening is offered in 13 out of 20 centres. PGD of translocations and other structural chromosome abnormalities is offered in all but one centre. The number of monogenic diseases offered varies considerably. In comparison to prenatal diagnosis PGD is more expensive. The majority of these costs are due to the IVF or ICSI procedure. The charges for PGD vary between about € 600 and € 4000. In 16 out of 20 centres the parents to be must sign an informed consent form. Copyright © 2001 John Wiley & Sons, Ltd.