bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two brothers with findings resembling congenital intrauterine infection‐like syndrome (pseudo‐TORCH syndrome)
Authors: Knoblauch Hans , Tennstedt Cornelia , Brueck Wolfgang , Hammer Hannes , Vulliamy Tom , Dokal Inderjeet , Lehmann Rüdiger , Hanefeld Folker , Tinschert Sigrid 
Published: June 2003

AbstractClinical, pathological, and X‐ray findings of two brothers with features resembling congenital intrauterine infection‐like syndrome are presented. Extensive screening for intrauterine infection was performed. Nevertheless all confirmatory tests were normal. Both brothers showed extensive intra‐ and extra‐cranial calcifications, thrombocytopenia, a septum pellucidum cyst, one‐sided paresis of the diaphragm, and metaphyseal changes on X‐ray scans resembling intrauterine infection. Within the first days of life, they developed seizures and died from severe cerebral hemorrhage. The MRI scan of the brain showed cerebellar hypoplasia in one of the boys, while the cerebellum had normal size in the other. No indication of a metabolic disorder, especially in calcium metabolism, was identified. Due to the clinical overlap with Hoyeraal‐Hreidarsson syndrome, mutations in the DKC1 gene (Xq28) and the hTR gene (RNA component of telomerase on chromosome 3q) have been excluded. The parents are non‐consanguineous and further family history was unremarkable. The findings in these boys overlap with features described in congenital intrauterine infection‐like syndrome (pseudo‐TORCH syndrome). © 2003 Wiley‐Liss, Inc.
Intrafamilial variability in the phenotypic expression of adenylosuccinate lyase deficiency: A report on three patients
Authors: Edery Patrick , Chabrier Stéphane , Ceballos‐Picot Irène , Marie Sandrine , Vincent Marie‐Françoise , Tardieu Marc 
Published: June 2003

AbstractWe report on the striking variable expression of adenylosuccinate lyase (ADSL) deficiency in three patients belonging to a family which originates from Portugal. ADSL deficiency is a rare autosomal recessive disorder of the de novo purine synthesis which results in accumulation of succinylpurines in body fluids. As a result, patients may have variable combinations of psychomotor retardation and/or regression, seizures, autistic features and cerebellar vermis hypoplasia. However, intrafamilial variable expression of the phenotype has not been documented to date in this disease and is not commonly observed in metabolic disorders. Here, while the proband had marked psychomotor regression and progressive cerebellar vermis atrophy, the other two affected patients presented mainly autistic features. Mutation analysis of the ADSL gene revealed the presence of a homozygous R426H mutation in this family. Finally, although ADSL deficiency is a rare disorder, this diagnosis should be considered and assessed using a simple urinary screening method for the presence of succinylpurines in any patient with mental retardation of unexplained origin. © 2003 Wiley‐Liss, Inc.
657del5 mutation in the gene for Nijmegen breakage syndrome (NBS1) in a cohort of Russian children with lymphoid tissue malignancies and controls
Authors: Resnick Igor B. , Kondratenko Irina , Pashanov Eugeni , Maschan Alexey A. , Karachunsky Alexander , Togoev Oleg , Timakov Andrey , Polyakov Alexander , Tverskaya Svetlana , Evgrafov Oleg , Roumiantsev Alexander G. 
Published: June 2003

AbstractNijmegen breakage syndrome (NBS, OMIM 251260) is a rare hereditary disease, characterized by immune deficiency, microcephaly, and an extremely high incidence of lymphoid tissue malignancies. The gene mutated in NBS, NBS1, was recently cloned from its location on chromosome 8q21. The encoded protein, nibrin (p95), together with hMre11 and hRad50, is involved in the double‐strand DNA break repair system. We screened two Russian cohorts for the 657del5 NBS1 mutation and found no carriers in 548 controls and two carriers in 68 patients with lymphoid malignancies: one with acute lymphoblastic leukemia (ALL) and one with non‐Hodgkin lymphoma (NHL). Several relatives of the second patient, who were carriers of the same mutation, had cancer (ALL, breast cancer, GI cancers). These preliminary data suggest that NBS1 mutation carriers can be predisposed to malignant disorders. © 2003 Wiley‐Liss, Inc.
Aberrant Pax1 and Pax9 expression in Jarcho‐Levin syndrome: Report of two Caucasian siblings and literature review
Authors: Bannykh Sergei I. , Emery Shawn Clark , Gerber Josef‐Karl , Jones Kenneth L. , Benirschke Kurt , Masliah Eliezer 
Published: June 2003

AbstractWe report two consecutive Caucasian male siblings of nonconsanguineous parents autopsied at 22 and 13 weeks gestational age both with prenatal diagnosis of Jarcho‐Levin syndrome (JLS). Segmentation anomalies of the vertebrae and ribs encompass a spectrum of syndromes with or without associated anomalies of other developmental fields, and include spondylothoracic dysostosis (STD), JLS, Casamassima‐Morton‐Nance (CMN) syndrome, and spondylocostal dysostosis (SCD), among others. In both these new JLS cases the autopsies confirmed that there were severe developmental alterations in the thoracic and vertebral skeleton (including “crab‐like” thorax), accompanied in the older fetus by renal defects. Because vertebral development is controlled by a limited number of master genes including Pax1 and Pax9, we analyzed protein expression from these genes in these two cases compared to age‐matched controls. Immunochemical analysis showed a significant reduction in levels of Pax1 and Pax9 protein expression in chondrocytes of the vertebral column. Implications for the etiology and pathogenesis of JLS and related disorders are discussed. © 2003 Wiley‐Liss, Inc.
Variations in the dopamine β‐hydroxylase gene are not associated with the autonomic disorders, pure autonomic failure, or multiple system atrophy
Authors: Cho Sonhae , Kim Chun‐Hyung , Cubells Joseph F. , Zabetian Cyrus P. , Hwang Dong‐Youn , Kim Jang‐Woo , Cohen Bruce M. , Biaggioni Italo , Robertson David , Kim Kwang‐Soo 
Published: June 2003

AbstractNorepinephrine (NE) is the major neurotransmitter of the sympathetic division of the autonomic nervous system (ANS). Recent findings of an association between human NE deficiency and variants at the dopamine β‐hydroxylase (DBH) gene [Kim et al., 2002] prompted us to investigate these markers in patients with autonomic disorders; 38 with orthostatic intolerance (OI), 26 with pure autonomic failure (PAF), and 39 with multiple system atrophy (MSA). Eighty‐eight normal controls were included in this study. In contrast to NE deficiency, allele frequency and genotype distribution of the genetic variants showed no differences between autonomic disease patients and controls. In addition, no DBH mutation was found that distinguished autonomic disease patients from controls, suggesting that genetic variants of the DBH gene are not associated with the autonomic diseases OI, PAF, and MSA. © 2003 Wiley‐Liss, Inc.
Brachyolmia and spinal stenosis
Authors: Mukamel Masza , Karmazyn Boaz , de Vries Liat , Horev Gadi , Shohat Mordechai 
Published: June 2003

AbstractBrachyolmia is a rare short‐trunk short stature skeletal dysplasia characterized by generalized platyspondyly without significant epiphyseal or metaphyseal changes in the long bones. This group of skeletal dysplasia is heterogeneous and four types have been differentiated on the basis of radiological and genetic findings. We report on two siblings with Hobaek‐type brachyolmia complicated by spinal stenosis. This combination has never been reported in the literature and suggests further genetic heterogeneity within brachyolmia. © 2003 Wiley‐Liss, Inc.
Is it a new syndrome or a clinical variability in cerebro‐oculo‐nasal syndrome?
Authors: Semerci C. Nur , Zorlu Pelin , Topal Yasar , Izbudak Izlem , Karacan Candemir , Balci Sevim 
Published: June 2003

AbstractWe present a male infant 2.5‐months old with asymmetric skull, anophthalmia, apparent hypertelorism, abnormal nares, unilateral cleft lip and palate, and structural abnormalities of the central nervous system. These findings are similar to cerebro‐oculo‐nasal syndrome except for the appearance of nose. This case is either a clinical variability in cerebro‐oculo‐nasal syndrome or a new entity. © 2003 Wiley‐Liss, Inc.
Typical facial clefting and constriction band anomalies: an unusual association in three unrelated patients
Authors: Taub Peter J. , Bradley James P. , Setoguchi Yoshio , Schimmenti Lisa , Kawamoto Henry K. 
Published: June 2003

AbstractThe amniotic band sequence is a rare congenital condition in which it is hypothesized that fibrous band of amniotic tissue result in variable soft tissue derangements. Other terms that have been used to describe this condition are amniotic band syndrome and amnion rupture sequence. Patients may present with craniofacial, thoracic, abdominal, and/or limb involvement. Previous reports have described the association between the amniotic band sequence and unusual patterns of facial clefting, as described by Tessier, that do not follow normal embryonic lines of fusion [Keller et al., 1978; Bagatin et al., 1997]. We describe three successive cases of the amniotic band sequence, which presented with rather typical facial clefts (cleft lip and palate) in unrelated patients. © 2003 Wiley‐Liss, Inc.
Population screening for cystic fibrosis: Knowledge and emotional consequences 18 months later
Authors: Gordon Claire , Walpole Ian , Zubrick Stephen R. , Bower Carol 
Published: June 2003

AbstractWe assessed cystic fibrosis (CF) knowledge and emotional consequences of CF population testing 18 months after screening was offered. Questionnaires were sent to 593 individuals and 353 responded (59.5%). All respondents had sound knowledge of CF disease, although carriers were more likely to correctly state the pattern of CF inheritance and CF carrier rate in Australia. Eleven of 47 carriers falsely believed they were only very likely to be carriers, while nearly a third of test‐negative individuals falsely believed they were definitely not carriers. Imprecise recall of the meaning of results may be due to memory loss over time, simplification of result meaning and minimization of risk. The Health Orientation Scale (HOS) was used to assess emotional consequences of CF carrier testing 18 months after testing. Both carriers and test‐negative individuals thought most carriers would experience more negative feelings than most non‐carriers. Carriers experienced less positive feelings about their test result compared to non‐carriers. Interestingly, the carriers' own feelings about their result were more positive compared to how they thought most carriers would feel. These results suggest that carriers experience minimal adverse psychological effects, although a negative social stigma may be attached to carrying the CF gene mutation. © 2003 Wiley‐Liss, Inc.
Homocysteine interference in neurulation: A chick embryo model
Authors: Afman L.A. , Blom H.J. , Van Der Put N.M.J. , Van Straaten H.W.M. 
Published: June 2003

AbstractBACKGROUNDPericonceptional folic acid supplementation reduces the occurrence and recurrence risk of neural tube defects (NTD). Mothers of children with NTD have elevated plasma homocysteine levels. Administering homocysteine to chick embryos is reported to cause 27% NTD. Therefore, elevated plasma homocysteine levels per se or a disturbed homocysteine metabolism may be teratogenic to the embryo and may interfere with neural tube closure. Our aim was to obtain a chick embryo model to explore the interference of homocysteine in neural tube closure.METHODSHomocysteine or saline was administered to chick embryos in ovo at 3 hr, 30 hr, and 60 hr of incubation and harvested at 74 hr. Homocysteine was then applied to chick embryos in vitro at a defined time window of four to six somites and followed for 6 hr.RESULTSHomocysteine administration to chick embryos in ovo resulted in several malformations but not in an increased number of NTDs. Homocysteine administration to chick embryos in vitro resulted in a transient, dose‐dependent widening of the anterior neuropore and closure delay of the rhombencephalic neuropore. After 16 hr of incubation the neural tube was closed.CONCLUSIONSThe in vitro chick embryo model appears a good model to explore the interference of a disturbed homocysteine metabolism in neurulation. Birth Defects Research (Part A) 67:421–428, 2003. © 2003 Wiley‐Liss, Inc.
Reduced SOD activity and increased neural tube defects in embryos of the sensitive but not of the resistant Cohen diabetic rats cultured under diabetic conditions
Authors: Weksler‐Zangen Sarah , Yaffe Pirhiya , Ornoy Asher 
Published: June 2003

AbstractBACKGROUNDThe role of reactive oxygen species in the etiology of diabetes‐induced anomalies was studied in a genetic model of nutritionally induced Type 2 diabetes mellitus: the Cohen diabetic sensitive (CDs) and resistant (CDr) rats. We have previously shown in this model that embryopathy may be induced by a combination of genetic and environmental factors. In our study we investigated the role of the antioxidant defense mechanism, genetic predisposition or environmental factors in embryos cultured under diabetic conditions.METHODSCDs, CDr and Sabra rat 11.5‐day old embryos were studied after 28 hr of culture in control (low glucose), high glucose, diabetic sub‐teratogenic, and diabetic teratogenic media. Embryos were monitored for growth retardation and congenital anomalies. Activity of superoxide dismutase (SOD) and catalase‐like (CAT) enzymes was measured in embryonic homogenates.RESULTSIn control medium, CDs embryos were significantly underdeveloped but exhibited no anomalies and SOD activity was not significantly different from that of CDr embryos. In high glucose medium, CDs embryos were smaller than CDr and Sabra embryos and smaller than CDs embryos cultured in control medium. Neural tube defects (NTD) were found predominantly in the CDs embryos starting from 14% in the high glucose medium and increasing to 29% in the sub‐teratogenic medium. In the teratogenic medium, <50% of the CDs and Sabra embryos were alive whereas all (100%) of the CDr embryos were alive. SOD activity significantly increased in CDs embryos when cultured in the high glucose medium but was significantly reduced in the sub‐teratogenic medium. SOD activity was increased significantly in the Sabra embryos cultured in the sub‐teratogenic medium but did not change in CDr embryos cultured in either one of the different culture media. CAT activity did not show any significant trend in either one of the rat strains or in any of the different culture conditions.CONCLUSIONSOur results suggest that genetic susceptibility plays an important role in inducing underdevelopment and NTD in cultured CDs embryos in sub‐teratogenic medium and in protecting the CDr embryos under the same conditions. The combination of a sub‐teratogenic environment with genetic susceptibility is sufficient to reduce the activity of SOD, hence decreasing the ability of the CDs embryos to cope with diabetic sub‐teratogenic environment and prevent NTD. Birth Defects Research (Part A) 67:429–437, 2003. © 2003 Wiley‐Liss, Inc.
Genetic dissection of hyperthermia‐induced neural tube defects in mice
Authors: Lundberg Yunxia Wang , Wing Michael J. , Xiong Wanfen , Zhao Jian , Finnell Richard H. 
Published: June 2003

AbstractBACKGROUNDMaternal hyperthermia has been shown to induce neural tube defects (NTD) in humans and in experimental animal systems. We report the first genetic dissection of maternal hyperthermia‐induced NTD in mice.METHODSAfter maternal exposure on E8.5 to 43°C water bath for 10 min, we observed exencephaly frequencies among E15.5–17.5 fetuses from the following crosses and backcrosses, SWV/Fnn(SWV)xSWV, C57BL/6J(C57)xC57, SWVxC57 (F1), F1xSWV and SWVxF1.RESULTSThe fetuses with maternal hyperthermia exposure developed exencephaly in a strain‐dependent manner and the exencephaly frequencies among the above crosses were 46.2, 14.3, 13.6, 11.3, and 27.0%, respectively, expressed over total live fetuses. The fetal death rates were 47.3, 24.6, 37.1, 4.3, and 35.5%, respectively, expressed over total implants.CONCLUSIONThe data demonstrate that a single fetal genetic locus, plus a maternal effect, have likely caused the strain differences in the susceptibility to hyperthermia‐induced exencephaly. A maternal effect alone may have caused the higher prenatal mortality rates in the SWVxF1 cross versus the reciprocal cross. Analysis of gender ratios among those affected from these crosses excludes an X‐ or Y‐linked effect in causing the higher numbers of affected females. Birth Defects Research (Part A) 67:409–413, 2003. © 2003 Wiley‐Liss, Inc.
Zinc influences the in vitro development of peri‐implantation mouse embryos
Authors: Hanna Lynn A. , Clegg Michael S. , Momma Tony Y. , Daston George P. , Rogers John M. , Keen Carl L. 
Published: June 2003

AbstractBACKGROUNDFor humans, it is estimated that over 70% of concepti are lost during early development. In culture, mouse peri‐implantation embryos can mimic development from the blastocyst to the egg cylinder stage of development, a period during which implantation occurs in vivo. We describe a novel application of this model to investigate nutritional factors that may influence this stage of development. We investigated the influence of zinc (Zn) deficiency on embryonic development at the time of embryo implantation.METHODSMouse blastocysts were cultured for 144 hr in low Zn, Zn‐replete or control medium.RESULTSEmbryos developed normally when they were cultured in the control and Zn‐replete media. Embryos cultured in the low Zn medium were significantly impaired in forming egg cylinder morphology. This was associated with a reduction in extraembryonic endoderm as determined by immunohistochemistry for markers of visceral and parietal endoderm and correlated with an increase in TUNEL positive cells in the low Zn group. There was no change in the frequency of cells positive for phosphorylated Histone H3, a marker for S‐phase, indicating that an increase in apoptosis was primarily responsible for the smaller size and reduction in extraembryonic endoderm. The increased cell death was not associated with an increase in reactive oxygen species (ROS) detected by dichlorodihydrofluorescein staining.CONCLUSIONSThese data support an important role for Zn in promoting differentiation and cell survival in the early embryo and suggest that sub‐optimal nutrition is an important factor that contributes to defects in primary germ layers and early embryonic loss. Birth Defects Research (Part A) 67: 414–420, 2003. © 2003 Wiley‐Liss, Inc.
Cleft‐palate lateral synechia syndrome: Insight into the phenotypic spectrum of Fryns syndrome?
Authors: Jaeger April , Kapur Raj , Whelan Michael , Leung Eric , Cunningham Michael 
Published: June 2003

AbstractBACKGROUNDIn 1972, Fuhrmann et al. (Humangenetik 1972;14:196–203) described a novel syndrome consisting of cleft palate (CP) and lateral synechiae (LS) between the palate and the floor of the mouth. This constellation of malformations, since denoted as cleft‐palate lateral synechiae syndrome (CPLS), is a rare syndrome; only five cases have been reported since the original description. Because of the paucity of recognized cases, little is known regarding the phenotypic spectrum of this presumably autosomal dominant condition.CASESWe report two unrelated patients who presented with remarkably similar phenotypic features, including multiple intraoral synechiae (filiforme intraalveolar bands), cleft palate, micrognathia, and redundant lower lip tissue. Their phenotypic findings indicate a diagnosis of CPLS; however, case 3 (the monozygotic twin of case 2) had classic phenotypic features of Fryns syndrome.CONCLUSIONSThis report presents two new cases of CPLS, and suggests that the CPLS phenotype may represent the mild end of the Fryns syndrome phenotypic spectrum. Supplementary material for this article can be found on the Birth Defects Research (Part A) website (http://www.interscience.wiley.com/jpages/1542‐0752/suppmat/67/fig5.xls) Birth Defects Research (Part A) 67:460–466, 2003. © 2003 Wiley‐Liss, Inc.
Cell‐cycle alterations underlie cyclophosphamide‐induced teratogenesis in the chick embryo
Authors: Heringová L. , Jelínek R. , Dostál M. 
Published: June 2003

AbstractBACKGROUNDCyclophosphamide (CP) embryotoxicity was documented in several studies on different experimental models. We investigate quantitatively the relationship between the embryotoxic effect of CP and the disturbance of the cell‐cycle using flow cytometry.METHODSChick embryos on Days 2–4 were treated with 0.5, 1, 2, 4, 8, and 16 μg doses of pure substance of CP by intraamniotic or subgerminal administration routes. Cell‐cycle analysis was carried out in the brain, limb buds, hearts, and facial outgrowths dissected from the embryos 6 hr after administration. Samples of nuclear suspensions were obtained by enzymatic and mechanical disintegration of solid tissues in collagenase‐dispase, followed by detergent and RNA‐ase mediated cytolysis. Nuclei were stained by ethidium bromide.RESULTSA dose‐dependent increase of S‐phase cells followed by decrement of G2M cell compartment was observed. The significant block of S‐phase cells, however, was not always associated with malformations. The degree of cell‐cycle disturbance was expressed more readily by the ratio G2M/S that demonstrated consistently the threshold character of both teratogenic and lethal effects.CONCLUSIONCP‐induced cytotoxicity manifested by dose‐dependent disturbance of cell‐cycle resulted in an overall depression of proliferation activity clearly associated with the occurrence of malformations and embryonic death. Although a non‐significant depression of mitotic activity appeared sufficient to produce malformations on Day 2, remarkably deeper disturbance was needed to interfere with the development of the embryos in more advanced stages. Changes in proliferation rate appear to be a primary and most important event in teratogenesis induced by general toxic agents. Birth Defects Research (Part A) 67438–443, 2003. © 2003 Wiley‐Liss, Inc.
Anticonvulsant teratogenesis 5: Observer bias in a cohort study
Authors: Harvey Elizabeth A. , Coull Brent A. , Holmes Lewis B. 
Published: June 2003

AbstractBACKGROUNDThe most common physical effects of prenatal exposure to the anticonvulsant drugs phenytoin and phenobarbital are midface and digit hypoplasia. These features are subjective in nature, which makes their detection vulnerable to any bias the examiner has, such as an increased expectation that the infant being examined has been exposed prenatally to an anticonvulsant drug. The purpose of this analysis was to determine whether or not there was evidence of observer bias in the detection of presumed anticonvulsant drug‐related physical features.METHODSThe presence or absence of three groups of features were compared: 1) midface hypoplasia, such as anteverted nostrils; 2) digit hypoplasia, e.g., tapered fingers, and 3) other features, e.g., prominent occiput, not known to be affected by exposure to anticonvulsants. These infants were examined by one masked physician examiner, using a study protocol, in three time periods: in two similar time periods, the masked examiner knew that one in four (25%) of the infants to be examined had been exposed to an anticonvulsant drugs; in the third time period, the chance was 50%.RESULTSThe frequencies of the subjective features of midface (odds ratio [OR] = 2.6) and digit hypoplasia (OR = 3.9), but not the other features, were significantly more common in the time periods when the masked examiner knew that there was a 50% chance of exposure to anticonvulsant drugs, compared to the time periods when there was a 25% chance.CONCLUSIONSThe findings suggest the effect of observer bias. In addition, there was evidence of context bias, meaning that a study that focuses on determining the presence of specific features will identify them more often. Birth Defects Research (Part A) 67:452–456, 2003. © 2003 Wiley‐Liss, Inc.