Range Of Birth Defects Research Articles

Limited upper mini-sternotomy approach for closed heart surgery in the newborns and infants.

The mini-sternotomy has become a common approach of choice for a wide range of congenital defects requiring minimally invasive surgery. Here, we aimed to present closed heart surgery results via limited upper mini-sternotomy in the newborn and infants. A total of 46 infants who underwent pulmonary artery banding, patent ductus arteriosus ligation, and aortopexy via limited upper mini-sternotomy between December 2017 and October 2020 were enrolled. Patients included 26 males and 20 females with ages ranging from 2days to 12months (median age 3.25 ± 0.9months). The weight ranged from 0.7kg to 8kg (median weight 3.6 ± 1.8kg). These patients were evaluated retrospectively in terms of clinical, preoperative, intraoperative, and postoperative parameters. Closed heart surgery procedures were corrected successfully without adverse events intraoperatively. The median operation time was 32min (32 ± 7min). The limited upper mini-sternotomy was performed on 46 patients, including the pulmonary banding (18 patients), PDA ligation (16 patients), and aortopexy (12 patients). No patients required conversion to full sternotomy or to extend the incision. Re-intervention to adjust the tightness of the band was required in 1 patient. There were 4 cases of mortality (8.6%). All four death cases had comorbidity and low birth weight (2500g or less). Limited upper mini-sternotomy is a technically feasible, safe, and effective approach that providing an adequately surgical view in closed heart surgery to reduce the invasiveness of the closed heart surgical repair via median sternotomy or thoracotomy approach.

Clinical and hematological aspects in pediatric patients diagnosed with Fanconi anemia – a single-center experience

Inherited bone marrow failure syndromes (IBMFS) are rare hematological disorders that characteristically associate physical abnormalities, ineffective hematopoiesis and pre­dis­position to cancer, accompanied by a range of congenital abnormalities. The most common are Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA) and Schwachman-Diamond syndrome (SDS). Most pa­tients have specific clinical features, making them very im­por­tant for establishing the correct diagnosis.

Leveraging a phenome-wide approach to identify novel exposure-birth defect associations: A proof of concept using maternal smoking and a spectrum of birth defects.

There are often questions about the impact of exposures on a range of birth defects, but there are few rigorous approaches for evaluating these associations. Using maternal smoking as an example we applied a phenome-wide association study (PheWAS) approach to evaluate the impact of this exposure on a comprehensive range of birth defects. Cases were obtained from the Texas Birth Defects Registry for the period 1999-2015. A total of 127 birth defects were examined. Maternal smoking at any time during the pregnancy was ascertained from the vital record. Data were randomly divided into discovery (60%) and replication (40%) partitions. Poisson regression models were run in the discovery partition, using a Bonferroni threshold of p < 3.9×10-4 . Birth defects passing that threshold in adjusted models were evaluated in the replication partition using p < 0.05 to determine statistical significance. Four birth defects were positively and significantly associated with maternal smoking in both partitions: cleft palate, anomalies of the pulmonary artery, other specified anomalies of the mouth and pharynx, and congenital hypertrophic pyloric stenosis. Obstructive defects of the renal pelvis and ureter showed consistent negative associations. All five defects exhibited significant dose-response relationships. We demonstrated that a statistically rigorous approach can be applied to birth defects registry data to examine the association between specified exposures and a range of birth defects. While we confirmed previously reported associations, others were not validated, likely due to misclassification in exposure based on vital records.

M\xfcllerian duct anomalies with term pregnancy: a case report

BackgroundMüllerian duct anomaly is a rare condition. Many cases remain unidentified, especially if asymptomatic. Thus, it is difficult to determine the actual incidence. Müllerian duct anomaly is associated with a wide range of gynecological and obstetric complications, namely infertility, endometriosis, urinary tract anomalies, and preterm delivery. Furthermore, congenital anomalies in pregnant mothers have a high risk of being genetically transmitted to their offspring.Case presentationWe report a case of a patient with unsuspected müllerian duct anomaly in a term pregnancy. A 33-year-old Malay woman with previously uninvestigated involuntary primary infertility for 4 years presented with acute right pyelonephritis in labor at 38 weeks of gestation. She has had multiple congenital anomalies since birth and had undergone numerous surgeries during childhood. Her range of congenital defects included hydrocephalus, for which she was put on a ventriculoperitoneal shunt; imperforated anus; and tracheoesophageal fistula with a history of multiples surgeries. In addition, she had a shorter right lower limb length with limping gait. Her physical examination revealed a transverse scar at the right hypochondrium and multiple scars at the posterior thoracic region, levels T10–T12. Abdominal palpation revealed a term size uterus that was deviated to the left, with a singleton fetus in a nonengaged cephalic presentation. The cervical os was closed, but stricture bands were present on the vagina from the upper third until the fornices posteriorly. She also had multiple rectal prolapses and strictures over the rectum due to previous anorectoplasty. An emergency cesarean delivery was performed in view of the history of anorectoplasty, vaginal stricture, and infertility. Intraoperative findings showed a left unicornuate uterus with a communicating right rudimentary horn.ConclusionMost cases of müllerian duct anomaly remain undiagnosed due to the lack of clinical suspicion and the absence of pathognomonic clinical and radiological characteristics. Because it is associated with a wide range of gynecological and obstetric complications, it is vital for healthcare providers to be aware of its existence and the role of antenatal radiological investigations in its diagnosis. The presence of multiple congenital abnormalities and a history of infertility in a pregnant woman should warrant the exclusion of müllerian duct anomalies from the beginning. Early detection of müllerian duct anomalies can facilitate an appropriate delivery plan and improve the general obstetric outcome.

A-190 Neuropsychological profile of adolescent with 22q11.2 Deletion Syndrome

Abstract Objective 22q11.2 deletion syndrome (22q11DS) is a genetic microdeletion disorder linked to various adverse medical and psychiatric outcomes affecting 1 in every 1,000 to 4,000 births. 22q11DS results from a meiotic deletion of DNA at the q11.2 site on chromosome 22, contributing to cognitive impairments resulting from a range of congenital anomalies. While data are inconsistent and the 22q11DS profile is incomplete—research suggests neuropsychological impairments with receptive language and attention. We describe the neuropsychological findings of a young woman with stronger than expected receptive language and atypical attention profile. Thus, we will highlight the cognitive profile of 22q11DS and the critical role of neuropsychological evaluation in clarifying cognitive performances. Methods This adolescent was diagnosed with 22q11DS at age 10, and various professionals made prior diagnoses of ADHD, ODD, Anxiety, ID, developmental delay, and learning delay without previous formal neuropsychological evaluation. Results Evaluation revealed low overall performances (WISCV- FSIQ = 66) with relative strengths on tasks of category fluency and receptive vocabulary, with stronger than expected receptive language. Her attention profile was not consistent with ADHD, although by history, ADHD criteria would have been met previously. Qualitatively, even with a low IQ, she did not present as someone with an ID. Conclusion This case of a young woman with 22q11DS with several prior diagnoses demonstrated a slightly atypical cognitive profile supporting the need for formal neuropsychological evaluation. Furthermore, the patterns of her performances add to the literature of 22q11 deletion syndromes and raise important questions regarding differences in cognitive development in individuals with 22q11DS.

Peroxynitrite is essential for the initiation of cytomegalovirus replication in vitro and in vivo

Human cytomegalovirus (HCMV) is a pathogenic beta-herpesvirus that establishes a lifelong infection in hosts. It causes significant morbidity and mortality in the immunocompromised and is associated with a range of birth defects following congenital infection. Current therapeutic approaches that target key viral proteins are toxic and antiviral drug resistance is common. Thus, targeting host genes and cellular pathways essential for HCMV infection offers an alternative strategy for the development of antivirals. Here we show that host oxidative/nitrosative stress responses to CMV are critical for virus replication. Oxidative/nitrosative stress occurs due to accumulation of reactive oxygen/nitrogen species (ROS/RNS). Using a range of ROS/RNS scavengers, we identified that peroxynitrite, a powerful oxidant and nitrating agent, dramatically promoted virus replication in both in vitro and in vivo models of CMV infection. HCMV rapidly induced production of intracellular peroxynitrite upon infection. Inhibition of peroxynitrite within the first 24 hours alleviates efficient HCMV infection in both cell-free and cell-associated infection systems, indicating that peroxynitrite may influence pathways necessary for HCMV entry and/or replication. Furthermore, peroxynitrite inhibition also inhibited HCMV reactivation from latency. Interestingly, the neurotransmitter and naturally-occurring peroxynitrite antagonist 5-hydroxytryptamine, commonly known as serotonin, also impinged on HCMV-induced peroxynitrite production and exhibited anti-HCMV activity. Thus, overall, our study demonstrates a novel role for intracellular peroxynitrite in CMV pathogenesis and implies that peroxynitrite could be targeted as a novel approach to inhibiting CMV infection.

The prevalence of birth defects among non-Hispanic Asian/Pacific Islanders and American Indians/Alaska Natives in Texas, 1999-2015.

There is considerable variability in the prevalence of birth defects among racial/ethnic groups. This study estimated birth defect prevalence among the less studied non-Hispanic (NH) Asian/Pacific Islander (PI) and American Indian/Alaska Native (AI/AN) populations in Texas relative to NH Whites. Data were obtained from the Texas Birth Defect Registry from 1999 to 2015 for deliveries to Texas-resident women who were NH White, NH Asian/PI, or AI/AN. This covers a live birth population of 2.6 million. Prevalence ratios and 95% confidence intervals (95% CIs) were calculated for NH Asian/PIs and AI/ANs (relative to NH Whites) for 44 birth defects using Poisson regression adjusting for maternal age. After adjustment there were 33 statistically significant prevalence ratios (aPRs). Among NH Asian/PIs, 23 defects had a lower aPR (0.38-0.86) and three defects had a higher aPR (1.19-2.50). AI/ANs had one defect with a significantly lower aPR (0.64) and six with a higher aPR (1.36-4.63). Non-Hispanic Asian/PIs generally have a lower prevalence ratio for many birth defects while AI/ANs have a higher prevalence ratio compared to NH Whites. These findings update the limited literature on this topic and warrant additional research to identify the true associations across a range of birth defects among these understudied racial/ethnic groups.

Cerebellar Agenesis: A Case to Remember

AbstractThere is a wide range of congenital anomalies of the posterior fossa. Of these, absence of cerebellar components seems to exist on a spectrum, much like anomalies seen with the more frequently encountered Dandy–Walker malformation. Here, we present a rare case of cerebellar agenesis, as seen at our institution, which falls on the extreme side of the spectrum. We also discuss normal and aberrant posterior fossa development, established or hypothesized genetic causes of such development, and implications on cerebellar function.

Pregnant women’s attitudes toward Zika virus vaccine trial participation

IntroductionAs Zika virus infection during pregnancy can cause a range of congenital anomalies, pregnant women may be a target population for vaccination in future outbreaks. Their inclusion in vaccine trials is critical to ensure safe and effective vaccines in pregnancy. Though many vaccine candidates are in development, pregnant women’s willingness to participate in Zika virus vaccine research is unknown. This study aims to describe pregnant women’s attitudes toward Zika virus vaccine research participation, as well as perceived barriers to and facilitators of enrollment. MethodsPregnant and recently postpartum women (n = 128) attending prenatal care at Massachusetts General Hospital completed surveys querying their willingness to participate in four hypothetical Zika virus vaccine trials and their motivations for participation. Demographics, information on prior Zika virus exposure, and vaccine acceptance were collected. ResultsMost women (77%) accepted participation in at least one hypothetical Zika virus vaccine trial, and women were significantly more likely to accept prospective enrollment in an inactivated vaccine trial compared to a live-attenuated vaccine trial (p-value <0.0001) or a nucleic acid-based vaccine trial (p-value <0.0444). Important motivators for participation included evidence from research with pregnant and non-pregnant people, a desire to protect the baby from Zika, perceptions of vaccine safety, and provider recommendation. ConclusionsA majority of women in this cohort were willing to participate in a Zika virus vaccine trial while pregnant, however, differences in acceptance exist between vaccine platforms. The high value placed on evidence by participants highlights the importance of gathering and communicating pregnancy-specific data to potential research participants and their providers. Women’s motivations for accepting research participation during pregnancy are important to inform the Zika virus vaccine research agenda, candidate prioritization, and trial design.

The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafish embryos

Primodos was a hormone pregnancy test used between 1958–1978 that has been implicated with causing a range of birth defects ever since. Though Primodos is no longer used, it’s components, Norethisterone acetate and Ethinyl estradiol, are used in other medications today including treatments for endometriosis and contraceptives. However, whether Primodos caused birth defects or not remains controversial, and has been little investigated. Here we used the developing zebrafish embryo, a human cell-line and mouse retinal explants to investigate the actions of the components of Primodos upon embryonic and tissue development. We show that Norethisterone acetate and Ethinyl estradiol cause embryonic damage in a dose and time responsive manner. The damage occurs rapidly after drug exposure, affecting multiple organ systems. Moreover, we found that the Norethisterone acetate and Ethinyl estradiol mixture can affect nerve outgrowth and blood vessel patterning directly and accumulates in the forming embryo for at least 24 hrs. These data demonstrate that Norethisterone acetate and Ethinyl estradiol are potentially teratogenic, depending on dose and embryonic stage of development in the zebrafish. Further work in mammalian model species are now required to build on these findings and determine if placental embryos also are affected by synthetic sex hormones and their mechanisms of action.

Associations between maternal periconceptional exposure to secondhand tobacco smoke and major birth defects

While associations between secondhand smoke and a few birth defects (namely, oral clefts and neural tube defects) have been noted in the scientific literature, to our knowledge, there is no single or comprehensive source of population-based information on its associations with a range of birth defects among nonsmoking mothers. We utilized data from the National Birth Defects Prevention Study, a large population-based multisite case-control study, to examine associations between maternal reports of periconceptional exposure to secondhand smoke in the household or workplace/school and major birth defects. The multisite National Birth Defects Prevention Study is the largest case-control study of birth defects to date in the United States. We selected cases from birth defect groups having >100 total cases, as well as all nonmalformed controls (10,200), from delivery years 1997 through 2009; 44 birth defects were examined. After excluding cases and controls from multiple births and whose mothers reported active smoking or pregestational diabetes, we analyzed data on periconceptional secondhand smoke exposure-encompassing the period 1 month prior to conception through the first trimester. For the birth defect craniosynostosis, we additionally examined the effect of exposure in the second and third trimesters as well due to the potential sensitivity to teratogens for this defect throughout pregnancy. Covariates included in all final models of birth defects with ≥5 exposed mothers were study site, previous live births, time between estimated date of delivery and interview date, maternal age at estimated date of delivery, race/ethnicity, education, body mass index, nativity, household income divided by number of people supported by this income, periconceptional alcohol consumption, and folic acid supplementation. For each birth defect examined, we used logistic regression analyses to estimate both crude and adjusted odds ratios and 95% confidence intervals for both isolated and total case groups for various sources of exposure (household only; workplace/school only; household and workplace/school; household or workplace/school). The prevalence of secondhand smoke exposure only across all sources ranged from 12.9-27.8% for cases and 14.5-15.8% for controls. The adjusted odds ratios for any vs no secondhand smoke exposure in the household or workplace/school and isolated birth defects were significantly elevated for neural tube defects (anencephaly: adjusted odds ratio, 1.66; 95% confidence interval, 1.22-2.25; and spina bifida: adjusted odds ratio, 1.49; 95% confidence interval, 1.20-1.86); orofacial clefts (cleft lip without cleft palate: adjusted odds ratio, 1.41; 95% confidence interval, 1.10-1.81; cleft lip with or without cleft palate: adjusted odds ratio, 1.24; 95% confidence interval, 1.05-1.46; cleft palate alone: adjusted odds ratio, 1.31; 95% confidence interval, 1.06-1.63); bilateral renal agenesis (adjusted odds ratio, 1.99; 95% confidence interval, 1.05-3.75); amniotic band syndrome-limb body wall complex (adjusted odds ratio, 1.66; 95% confidence interval, 1.10-2.51); and atrial septal defects, secundum (adjusted odds ratio, 1.37; 95% confidence interval, 1.09-1.72). There were no significant inverse associations observed. Additional studies replicating the findings are needed to better understand the moderate positive associations observed between periconceptional secondhand smoke and several birth defects in this analysis. Increased odds ratios resulting from chance (eg, multiple comparisons) or recall bias cannot be ruled out.

Akabane virus infection.

Akabane virus is a Culicoides-borne orthobunyavirus that is teratogenic to the fetus of cattle and small ruminant species. Depending upon the stage of gestation atwhich infection occurs, and the length of gestation of the mammalian host, a range of congenital defects may be observed. The developing central nervous system is usually the most severely affected, with hydranencephaly and arthrogryposis most frequently observed. Less commonly, some strains of Akabane virus can cause encephalitis in the neonate or, rarely, adult cattle. Akabane viruses are known to be widespread in temperate and tropical regions of Australia, Southeast Asia, the Middle East and some African countries. Disease is infrequently observed in regions where this virus is endemic and the presence of the virus remains unrecognised in the absence of serological surveillance. In some Asian countries, vaccines are used to minimise the occurrence of disease.

Transcriptomic changes in mouse embryonic stem cells exposed to thalidomide during spontaneous differentiation.

Thalidomide is a potent developmental toxicant that induces a range of birth defects, notably severe limb malformations. To unravel the molecular mechanisms underpinning the teratogenic effects of thalidomide, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on the differentiation of mouse embryonic stem cells (mESCs), and published the major findings in a research article entitled “Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells” [1]. The data presented herein contains complementary information related to the aforementioned research article.

Minimally invasive atrial septal defect closure: what is that?

In this issue, Nezafati et al. [1] present their centre’s experience on off-pump atrial septal defect closure. Interestingly, they opted for caval inflow occlusion. Technological advances enable treatment for a wide range of congenital defects with often excellent results. As a result, both children and adults with congenital heart defects can now expect better outcomes. In recent years, however, surgical techniques have also centred around reduction of trauma and postoperative recovery time and also improvement of cosmetic results. However, these techniques have had selective application in congenital cardiac surgery when compared with adults. Open heart procedures for congenital lesions have been largely confined to operations where an intracardiac repair is carried out through the right atrium. A conventional full sternotomy approach for treatment of ‘simple’ lesions can now largely be avoided; instead, approaches vary from an anterior thoracotomy, inframammary thoracotomy and posterior thoracotomy to a limited inferior sternotomy. Nowadays, Atrial septal communications can usually be closed by an interventional cardiologist, unless morphological features are unfavourable. I would call this a true minimally invasive method. Any other attempt is rather ‘minimal access’ surgery. For the latter, a range of approaches are currently used: cardiopulmonary bypass (CPB)-assisted operations with minimal thoracotomies or ‘hybrid procedures’. The term ‘hybrid procedures’ refers to the combined use of direct surgical access to cardiac structures and catheterbased techniques to treat cardiac defects [2]. Nezafati et al. [1] describe a technique that lies somewhat in between. Even though any percutaneous programme is costly and requires a specific setup, Butera et al. [3] showed in a summary of data from studies comparing surgical versus percutaneous closure of atrial septal defects that treatment by a percutaneous approach has a significantly lower rate of either total or major early post-procedural complications compared with surgery. Economical issues are, however, a concern in many countries. In part, this seemed to have led the colleagues to aim for avoidance of CPB. Even though they report on a low overall complication rate, I would personally not advocate the use of this approach unless patients are carefully informed and selected, and all team members are acquainted in detail with all procedural steps. It is of note, however, that, for instance, mitral valve surgery is occasionally done on the beating heart too [4]. Personally, potential neurological sequelae and assurance of 100% closure of any interatrial connection would be my major concern. The described technique must be carried out within a limited time, both for visualizing the atrial septal defect margins and subsequent closure. It is of note that none of the defects could be closed with a patch. With regard to the surgical approach, I am in favour of staying well away from future breast tissue in prepubescent patients, especially in female patients. We have highlighted this issue and have since only opted for a midaxillary incision in young patients [5]. Beyond puberty, we cannulate the jugular vein and the femoral vessels, and perform only a very limited anterolateral thoracotomy. It will be interesting to see whether the described contribution triggers further applications. If cardiologists fail to close an atrial septal defect, a surgeon ought to offer the patient a safe and reliable treatment, keeping cosmetic aspects in mind.

Current position of phenobarbital in epilepsy and its future

This article reviews the current position of phenobarbital using articles published since 2000 and speculates on its likely future contribution to epilepsy care. Over the last decade there have been no major double-blind randomized placebo-controlled or comparative trials with phenobarbital. Previous studies have suggested that phenobarbital is as effective in monotherapy as phenytoin and carbamazepine. Several observational studies undertaken in developing countries over the last decade have confirmed its efficacy and safety for the common epilepsies. This was particularly so in the substantial demonstration project undertaken in rural China under the auspices of the World Health Organization in partnership with the International League Against Epilepsy and International Bureau for Epilepsy. Phenobarbital is still widely used for neonatal and childhood seizures and for drug-resistant convulsive and nonconvulsive status epilepticus. Recent data have confirmed in a prospective cohort of women taking phenobarbital as monotherapy that the drug can be associated with a range of congenital defects in exposed infants. Much effort has gone into exploring the apparent contradiction of higher withdrawal rates due to cognitive and behavioral side effects in studies undertaken in developed countries but not in those sited in the developing world. A raft of data over the last 10 years, including a systematic review, showed no important differences between the tolerability of phenobarbital compared to that with other antiepileptic drugs. Finally, cognitive test scores and mood ratings in 136 people with epilepsy receiving phenobarbital for a year were similar to those in 137 age-, sex-, and education-matched controls in a number of Chinese villages. Indeed, there were some cognitive gains in the patients possibly due to improved seizure control. Phenobarbital is still the most cost-effective pharmacologic treatment for epilepsy. All these data predict a healthy future for phenobarbital, particularly in helping to close the treatment gap in low- and middle-income countries during its second century of clinical use.

Is maternal parity an independent risk factor for birth defects?

Although associations between maternal parity and birth defects have been observed previously, few studies have focused on the possibility that parity is an independent risk factor for birth defects. We investigated the relation between levels of parity and a range of birth defects, adjusting each defect group for the same covariates. We included infants who had an estimated delivery date between 1997 and 2007 and participated in the National Birth Defects Prevention Study, a multisite case-control study. Cases included infants or fetuses belonging to 38 phenotypes of birth defects (n = 17,908), and controls included infants who were unaffected by a major birth defect (n = 7173). Odds ratios (ORs) were adjusted for 12 covariates using logistic regression. Compared with primiparous mothers, nulliparous mothers were more likely to have infants with amniotic band sequence, hydrocephaly, esophageal atresia, hypospadias, limb reduction deficiencies, diaphragmatic hernia, omphalocele, gastroschisis, tetralogy of Fallot, and septal cardiac defects, with significant ORs (1.2 to 2.3). Compared with primiparous mothers, multiparous mothers had a significantly increased risk of omphalocele, with an OR of 1.5, but had significantly decreased risk of hypospadias and limb reduction deficiencies, with ORs of 0.77 and 0.77. Nulliparity was associated with an increased risk of specific phenotypes of birth defects. Most of the phenotypes associated with nulliparity in this study were consistent with those identified by previous studies. Research into biologic or environmental factors that are associated with nulliparity may be helpful in explaining some or all of these associations.

Molecular Mechanisms in 22q11 Deletion Syndrome

It is now well recognized that as well as having a characteristic facial dysmorphology and a range of congenital abnormalities, individuals with chromosome 22q11 deletion syndrome (22q11DS) have a greatly increased risk of developing psychosis, in particular schizophrenia. The majority of deletions span a large 3Mb region at 22q11. However, the presence of affected individuals carrying smaller deletions have not been sufficient to satisfactorily reduce the critical region for the behavioral phenotype beyond a ~1.5Mb region that contains at least 28 genes. By having a shared genetic variant that greatly increases risk to psychosis, individuals with 22q11DS are a relatively homogeneous population to study psychiatric disease. Despite this, the large volume of research performed over the last 15 years suggest that the mechanism by which haploinsufficiency at 22q11 increases risk to psychiatric illness is likely to be complex and it remains uncertain why individuals carrying identical 22q11 deletions can present with such a wide range of neuropsychiatric phenotypes. This review will therefore consider the ways in which deletions at 22q11 are expected to increase risk to develop psychiatric disease by summarizing the work that has been done to investigate three of the most likely disease causing mechanisms: (a) gene dosage sensitivity; (b) unmasking of recessive alleles or functional polymorphism; and (c) position effect.

Methodology matters: IVF versus ICSI and embryonic gene expression

The use of assisted reproduction treatment, especially intracytoplasmic sperm injection (ICSI), is now linked to a range of adverse consequences, the aetiology of which remains largely undefined. Our objective of this study was to determine differences in gene expression of blastocysts generated by ICSI as well as ICSI with artificial oocyte activation (ICSI-A) versus the less manipulative IVF, providing fundamental genetic information that can be used to aid in the diagnosis or treatment of those adversely affected by assisted reproduction treatment, as well as stimulate research to further refine these techniques. Murine blastocysts were generated by ICSI, ICSI-A and IVF, and processed for a microarray-based analysis of gene expression. Ten blastocysts were pooled for each procedure and three independent replicates generated. The data were then processed to determine differential gene expression and to identify biological pathways affected by the procedures. In blastocysts derived by ICSI versus IVF, the expression of 197 genes differed ( P < 0.01). In blastocysts derived by ICSI-A versus IVF and ICSI-A versus ICSI, the expression of 132 and 65 genes differed respectively ( P < 0.01). Procedural-induced changes in genes regulating specific biological pathways revealed some consistency to known adverse consequences. Detailed investigation of procedure-specific dysfunction is therefore warranted. The use of reproductive manipulations including intracytoplasmic sperm injection (ICSI) has become increasingly linked to a range of adverse consequences, the cause of which remains largely undefined. Adverse effects include complications of pregnancy and parturition in the mother, as well as a range of birth defects in her offspring. The objective of this study was to determine differences in the gene expression of blastocysts generated by the major reproductive techniques: ICSI and ICSI with artificial oocyte activation (ICSI-A) versus the less manipulative IVF. In ICSI and ICSI-A, the head of a spermatozoon is directly injected into the mouse oocyte. Determination of differences in gene expression will provide novel information that can be used to aid in the diagnosis or treatment of those adversely affected by these procedures, as well as to stimulate research to further refine these techniques. Blastocysts were generated by performing ICSI, ICSI-A and IVF, using gametes collected from mice. The blastocysts were then processed for a microarray-based analysis of gene expression. Ten blastocysts were pooled for each procedure and three independent replicates generated. The data were then processed to determine differential gene expression and to identify biological pathways affected by procedure. Procedural-induced changes in the gene expression of blastocysts were observed. Classification of differentially regulated genes into biological pathways revealed consistency to known adverse consequences. Further investigation of procedure-specific treatment-induced dysfunction is needed.

Genetic abnormalities of chromosome 22 and the development of psychosis

A microdeletion at chromosome 22q11 is the most frequently known interstitial deletion found in humans, occurring in approximately one of every 4000 live births. Its occurrence is associated with a characteristic facial dysmorphology, a range of congenital abnormalities, and psychiatric problems, especially schizophrenia. The prevalence of psychosis in those with 22q11 deletion syndrome is high (30%), suggesting that haploinsufficiency of a gene or genes in this region may confer a substantially increased risk. In addition, several studies provide evidence for linkage to schizophrenia on 22q, suggesting that a gene in this region could confer susceptibility to schizophrenia in nondeleted cases. Recent studies have provided compelling evidence that haploinsufficiency of TBX1 is likely to be responsible for many of the physical features associated with the deletion. However, although a number of genes have been implicated as possible schizophrenia susceptibility loci, further confirmatory studies are required.