bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay between heredity and environment in the recent explosion of type 1 childhood diabetes mellitus
Authors: Laron Zvi 
Published: October 2002

AbstractThe fast increase in the incidence of childhood type 1 diabetes mellitus (T1DM) that cannot be explained by changes in the genetic susceptibility, led us to look for environmental causes. To test the hypothesis that the initiation of the autoimmune process of childhood T1DM in genetically susceptible subjects begins in the perinatal period by a viral infection, we studied the seasonal variations in the month of birth of several cohorts of patients compared to the general population. Population groups with high or low T1DM incidence were analyzed separately by t‐test and the Cosinor methods. In areas with populations with a high incidence (Israeli Jews, Sicily, Sardinia, Slovenia, Germany) we found that the children (in Sicily also young adults) who subsequently developed T1DM, have a higher incidence of births in the summer months than in other seasons of the year, a mirror image of the seasonality of the clinical onset of disease. This pattern differed significantly from the seasonality of the total live births in the same populations. In populations with a low T1DM incidence, (China, Japan and Cuba) no seasonality of month of birth was found. Similar findings have been reported, from five counties in the U.K. and the Netherlands. It is hypothesized that mothers who become pregnant during the period of yearly viral epidemics transmit to the fetus, either a virus or antiviral antibodies, which determine whether an autoimmune process against the pancreatic β is initiated or whether the fetus is protected against that process. © 2002 Wiley‐Liss, Inc.
Environmental factors in the etiology of type 1 diabetes
Authors: Åkerblom Hans K. , Vaarala Outi , Hyöty Heikki , Ilonen Jorma , Knip Mikael 
Published: October 2002

AbstractType 1 diabetes is considered to be an autoimmune disease in which T lymphocytes infiltrate the islets of pancreas and destroy the insulin producing beta cell population. Besides antigen specificity, the quality of immune reactivity against islet cell antigen(s) is an important determinant of the beta cell destruction. Much evidence indicates that the function of the gut immune system is central in the pathogenesis, as the regulation of the gut immune system may be aberrant in type 1 diabetes. The role of virus infections in the pathogenesis of type 1 diabetes has been supported by substantial new evidence suggesting that one virus group, enteroviruses, may trigger the beta‐cell damaging process in a considerable proportion of patients. The latest evidence comes from studies indicating the presence of viral genome in diabetic patients and from prospective studies confirming epidemiological risk effect. If this association holds still true in ongoing large‐scale studies, intervention trials should be considered to confirm causality. Of the dietary putative etiological factors, cow's milk proteins have received the main attention. Many studies indicate an association between early exposure to dietary cow's milk proteins and an increased risk of type 1 diabetes. The question will be answered by a large scale, prospective, randomized, international intervention trial. Another dietary factor in need of more studies is the deficiency of vitamin D. Among toxins, N‐nitroso compounds are the main candidates. An interaction of genetic and environmental factors is important in evaluating the possible role of a certain environmental factor in the etiology of type 1 diabetes. © 2002 Wiley‐Liss, Inc.
A 52‐kb deletion in the SOST‐MEOX1 intergenic region on 17q12‐q21 is associated with van Buchem disease in the Dutch population
Authors: Staehling‐Hampton Karen , Proll Sean , Paeper Bryan W. , Zhao Lei , Charmley Patrick , Brown Analisa , Gardner Jessica C. , Galas David , Schatzman Randall C. , Beighton Peter , Papapoulos Socrates , Hamersma Herman , Brunkow Mary E. 
Published: October 2002

AbstractVan Buchem disease is an autosomal recessive sclerosing bone dysplasia characterized by skeletal hyperostosis, overgrowth of the mandible, and a liability to entrapment of the seventh and eighth cranial nerves. The genetic determinant maps to chromosome 17q12‐q21. We refined the critical interval to the < 1‐Mb region between D17S2250 and D17S2253 in 15 affected individuals, all of whom shared a common disease haplotype. Furthermore, we report here the identification of a 52‐kb deletion located within the interval and encompassing D17S1789 that is 100% concordant with the disorder. Although the deletion itself does not appear to disrupt the coding region of any known or novel gene(s), the closest flanking genes are MEOX1 on the proximal side, and SOST on the distal side of the deletion. MEOX1 is known to be important for the development of the axial skeleton, whereas the SOST gene is the determinant of sclerosteosis, a disorder that shares many features with van Buchem disease, thus raising the possibility that van Buchem disease results from dysregulation of the expression of one or both of these genes. © 2002 Wiley‐Liss, Inc.
Genetic risk assessment in carrier testing for spinal muscular atrophy
Authors: Ogino Shuji , Leonard Debra G.B. , Rennert Hanna , Ewens Warren J. , Wilson Robert B. 
Published: October 2002

AbstractAs evidenced by the complete absence of a functionally critical sequence in exon 7, approximately 94% of individuals with clinically typical spinal muscular atrophy (SMA) lack both copies of the SMN1 gene at 5q13. Hence most carriers have only one copy of SMN1. Combining linkage and dosage analyses for SMN1, we observed unaffected individuals who have two copies of SMN1 on one chromosome 5 and zero copies of SMN1 on the other chromosome 5. By dosage analysis alone, such individuals, as well as carriers of non‐deletion disease alleles, are indistinguishable from non‐carrier individuals. We report that approximately 7% of unaffected individuals without a family history of SMA have three or four copies of SMN1, implying a higher frequency of chromosomes with two copies of SMN1 than previously reported. We present updated calculations for disease and non‐disease allele frequencies and we describe how these frequencies can be used for genetic risk assessment in carrier testing for SMA. © 2002 Wiley‐Liss, Inc.
Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile‐X knockout mice
Authors: Irwin Scott A. , Idupulapati Madhuri , Gilbert Molly E. , Harris Jennifer B. , Chakravarti Aparna B. , Rogers Erica J. , Crisostomo Ralph A. , Larsen Brian P. , Mehta Amit , Alcantara C.J. , Patel Biraju , Swain Rodney A. , Weiler Ivan Jeanne , Oostra Ben A. , Greenough William T. 
Published: October 2002

AbstractFragile‐X syndrome is a common form of mental retardation resulting from the inability to produce the fragile‐X mental retardation protein. The specific function of this protein is unknown; however, it has been proposed to play a role in developmental synaptic plasticity. Examination of human brain autopsy material has shown that fragile‐X patients exhibit abnormalities in dendritic spine structure and number, suggesting a failure of normal developmental dendritic spine maturation and pruning in this syndrome. Similar results using a knockout mouse model have previously been described; however, it was noted in retrospect that the mice used in that study may have carried a mutation for retinal degeneration, which may have affected cell morphology in the visual cortex of those animals. In this study, dendritic spines on layer V pyramidal cells of visual cortices, taken from fragile‐X knockout and wild‐type control mice without the retinal degeneration mutation and stained using the Golgi‐Cox method, were investigated for comparison with the human condition. Quantitative analyses of the lengths, morphologies, and numbers of dendritic spines, as well as amount of dendritic arbor and dendritic branching complexity, were conducted. The fragile‐X mice exhibited significantly more long dendritic spines and significantly fewer short dendritic spines than control mice. Similarly, fragile‐X mice exhibited significantly more dendritic spines with an immature‐like morphology and significantly fewer with a more mature type morphology. However, unlike the human condition, fragile‐X mice did not exhibit statistically significant dendritic spine density differences from controls. Fragile‐X mice also did not demonstrate any significant differences from controls in dendritic tree complexity or dendritic arbor. Long dendritic spines with immature morphologies are characteristic of early development or a lack of sensory experience. These results are similar to those found in the human condition and further support a role for the fragile‐X mental retardation protein specifically in normal dendritic spine developmental processes. They also support the validity of these mice as a model of fragile‐X syndrome. © 2002 Wiley‐Liss, Inc.
Complex relationship between Parkin mutations and Parkinson disease
Authors: West Andrew , Periquet Magali , Lincoln Sarah , Lücking Christoph B. , Nicholl David , Bonifati Vincenzo , Rawal Nina , Gasser Thomas , Lohmann Ebba , Deleuze Jean‐François , Maraganore Demetrius , Levey Allan , Wood Nick , Dürr Alexandra , Hardy John , Brice Alexis , Farrer Matt 
Published: October 2002

AbstractMutations in the Parkin gene cause juvenile and early onset Parkinsonism. While Parkin‐related disease is presumed to be an autosomal‐recessive disorder, cases have been reported where only a single Parkin allele is mutated and raise the possibility of a dominant effect. In this report, we re‐evaluate twenty heterozygous cases and extend the mutation screening to include the promoter and intron/exon boundaries. Novel deletion, point and intronic splice site mutations are described, along with promoter variation. These data, coupled with a complete review of published Parkin mutations, confirms that not only is recessive loss of Parkin a risk factor for juvenile and early onset Parkinsonism but that Parkin haploinsufficiency may be sufficient for disease in some cases. © 2002 Wiley‐Liss, Inc.
Small familial supernumerary ring chromosome 2: FISH characterization and genotype‐phenotype correlation
Authors: Giardino Daniela , Finelli Palma , Russo Silvia , Gottardi Giulietta , Rodeschini Ornella , Atza Maria Gabriella , Natacci Federica , Larizza Lidia 
Published: October 2002

AbstractA child and his mother were found to be mosaic for a small supernumerary marker chromosome (SMC) that was identified and characterized by means of fluorescent in situ hybridization. The marker chromosome was derived from the pericentromeric region of chromosome 2; the involvement of proximal 2q was determined by YAC probes. The proband was referred because of psychotic illness and mild mental retardation, whereas his mother presented only minor dysmorphisms. There are only a few published reports concerning SMC(2) or proximal 2q trisomy. We reviewed the previously reported cases in an attempt to establish genotype‐phenotype correlations, which are particularly important when SMCs are identified in prenatal diagnosis. © 2002 Wiley‐Liss, Inc.
Tardive dystonia and genetic polymorphisms of cytochrome P4502D6 and dopamine D2 and D3 receptors: A preliminary finding
Authors: Mihara Kazuo , Kondo Tsuyoshi , Higuchi Hisashi , Takahashi Hitoshi , Yoshida Keizo , Shimizu Tetsuo , Kaneko Sunao 
Published: October 2002

AbstractTardive dystonia is an uncommon but intractable and distressing complication of neuroleptic treatment. It is suggested that individual predisposing vulnerability plays a major role in the development of the side effect. This study aimed to investigate relationship tardive dystonia and several genetic factors such as polymorphism of cytochrome P4502D6, and receptor polymorphisms of dopamine D2 (TaqI A and −141C Ins/Del polymorphisms) and D3 (Ser9Gly polymorphism). Nine patients with tardive dystonia were genotyped for these genetic polymorphisms. No specific genotypes or alleles were overpresented in the patients. This study suggests that these polymorphisms are not related to the development of tardive dystonia. © 2002 Wiley‐Liss, Inc.
Brain volumes in familial and non‐familial schizophrenic probands and their unaffected relatives
Authors: McDonald Colm , Grech Anton , Toulopoulou Timothea , Schulze Katja , Chapple Ben , Sham Pak , Walshe Muriel , Sharma Tonmoy , Sigmundsson Thordur , Chitnis Xavier , Murray Robin M. 
Published: October 2002

AbstractStructural brain abnormalities are consistently reported in schizophrenic subjects but the etiology of these abnormalities remains unclear. We tested the contribution of genetic predisposition and obstetric complications to the structural brain abnormalities found in schizophrenic probands and their relatives. MRI scans were carried out on 35 schizophrenic probands from families multiply affected with the disorder, and 63 of their unaffected relatives, including 10 parents who appeared to transmit genetic risk to their children; as well as 31 schizophrenic probands from families with no other affected members, 33 of their unaffected relatives; and finally 68 controls. Volumetric measurements of whole brain, lateral ventricles, third ventricle, cerebellum, and temporal lobes were completed for each subject. The impact of obstetric complications on brain structure was assessed across the gradient of presumed genetic predisposition. Both groups of schizophrenic probands displayed enlargement of the lateral and third ventricles, and there was a gradient of ventricular enlargement amongst the unaffected relatives in proportion to their likelihood of carrying schizophrenic genes. Ventricular enlargement was largely confined to males in both probands and unaffected relatives. Obstetric complications were associated with ventricular enlargement only in the familial probands. Non‐familial probands displayed reduced volume of the temporal lobes bilaterally. In families with several schizophrenic members, ventricular enlargement is a marker for genetic liability, particularly in males. Individuals inheriting the susceptibility to schizophrenia appear particularly prone to develop ventricular enlargement in response to obstetric complications. © 2002 Wiley‐Liss, Inc.
Spatial working memory deficits in schizophrenia patients and their first degree relatives from Palau, Micronesia
Authors: Myles‐Worsley Marina , Park Sohee 
Published: October 2002

AbstractSpatial working memory deficits associated with dorsolateral prefrontal dysfunction have been found in Caucasian samples of schizophrenia patients and their first‐degree relatives. This study evaluated spatial working memory function in affected and unaffected members of multiplex schizophrenia families from the Republic of Palau to determine whether the spatial working memory deficits associated with schizophrenia extend to this non‐Caucasian population. Palau is an isolated island nation in Micronesia with an elevated prevalence of schizophrenia and an aggregation of cases in large multigenerational families. Our objective was to evaluate the potential for spatial working memory function to serve as one of multiple endophenotypes in a genetic linkage study of these Palauan schizophrenia families. A spatial delayed response task requiring resistance to distraction and a sensorimotor control task were used to assess spatial working memory in 32 schizophrenia patients, 28 of their healthy first‐degree relatives, and 19 normal control subjects. Schizophrenia patients and their relatives were significantly less accurate than normal control subjects on the spatial delayed response task but not on the sensorimotor control task. On both tasks, patients and relatives were slower to respond than the normal controls. There were no age or gender effects on accuracy, and working memory performance in schizophrenia patients was not significantly correlated with medication dosage. In summary, spatial working memory deficits that have been found in Caucasian schizophrenia patients and relatives were confirmed in this isolated Pacific Island family sample. These results suggest that spatial working memory deficits may be a potentially useful addition to the endophenotypic characterization of family members to be used in a comprehensive genome wide linkage analysis of these Palauan families. © 2002 Wiley‐Liss, Inc.
Alteration of branch site consensus sequence and enhanced pre‐mRNA splicing of an NMDAR1 intron not associated with schizophrenia
Authors: Hammond Linda , Castanotto Daniela , Rice Sharmon R. , Nimgaonkar Vishwajit L. , Wirshing Donna A. , Rossi John J. , Heston Leonard L. , Sobell Janet L. 
Published: October 2002

AbstractAberrant splicing of pre‐mRNA is recognized to account for a significant minority of disease‐causing mutations. The N‐methyl‐D‐aspartate receptor (NMDA) subunit gene R1 (NMDAR1) is alternatively spliced to produce eight length variants. In an examination of the NMDAR1 as a candidate gene in schizophrenia, a presumed microdeletion/insertion (del/ins) was observed in intron 10 of an African‐American male near a weak putative branch‐site consensus sequence. Although exon 10 is not known to be alternatively spliced, the del/ins was posited to alter splicing efficiency. If splicing were abolished and intron retention occurred, an in‐frame translation product of more than 250 amino acids was predicted. To explore splicing efficiency, mini genes were examined through primer‐extension analyses in NIH293 embryonic kidney cell cultures. Rather than disruption of splicing, the del/ins allele exhibited a fivefold enhancement in splicing. In an association analysis with additional schizophrenic cases and unaffected controls, all of African‐American descent, the mutant allele was observed at equivalent frequencies. A family study also did not support cosegregation of the variant allele with psychiatric disease. © 2002 Wiley‐Liss, Inc.
Mitochondrial disorders: genetics, counseling, prenatal diagnosis and reproductive options
Authors: Thorburn David R. , Dahl Hans‐Henrik M. 
Published: October 2002

AbstractMost patients with mitochondrial disorders are diagnosed by finding a respiratory chain enzyme defect or a mutation in the mitochondrial DNA (mtDNA). The provision of accurate genetic counseling and reproductive options to these families is complicated by the unique genetic features of mtDNA that distinguish it from Mendelian genetics. These include maternal inheritance, heteroplasmy, the threshold effect, the mitochondrial bottleneck, tissue variation, and selection. Although we still have much to learn about mtDNA genetics, it is now possible to provide useful guidance to families with an mtDNA mutation or a respiratory chain enzyme defect. We describe a range of current reproductive options that may be considered for prevention of transmission of mtDNA mutations, including the use of donor oocytes, prenatal diagnosis (by chorionic villus sampling or amniocentesis), and preimplantation genetic diagnosis, plus possible future options such as nuclear transfer and cytoplasmic transfer. For common mtDNA mutations associated with mitochondrial cytopathies (such as NARP, Leigh Disease, MELAS, MERRF, Leber's Hereditary Optic Neuropathy, CPEO, Kearns‐Sayre syndrome, and Pearson syndrome), we summarize the available data on recurrence risk and discuss the relative advantages and disadvantages of reproductive options. © 2001 Wiley‐Liss, Inc.
Advances in the genetics of progressive myoclonus epilepsy
Authors: Delgado‐Escueta A.V. , Ganesh Subramaniam , Yamakawa Kazuhiro 
Published: October 2002

AbstractThe genetic progressive myoclonus epilepsies (PMEs) are clinically characterized by the triad of stimulus sensitive myoclonus (segmental lightning like muscular jerks), epilepsy (grand mal and absences) and progressive neurologic deterioration (dementia, ataxia, and various neurologic signs depending on the cause). Etiologically heterogenous, PMEs are rare and mostly autosomal recessive disorders, with the exception of autosomal dominant dentatorubral‐pallidoluysian atrophy and mitochondrial encephalomyopathy with ragged red fibers (MERRF). In the last five years, specific mutations have been defined in Lafora disease (gene for laforin or dual specificity phosphatase in 6q24), Unverricht‐Lundborg disease (cystatin B in 21q22.3), Jansky‐Bielschowsky ceroid lipofuscinoses (CLN2 gene for tripeptidyl peptidase 1 in 11q15), Finnish variant of late infantile ceroid lipofuscinoses (CLN5 gene in 13q21‐32 encodes 407 amino acids with two transmembrane helices of unknown function), juvenile ceroid lipofuscinoses or Batten disease (CLN3 gene in 16p encodes 438 amino acid protein of unknown function), a subtype of Batten disease and infantile ceroid lipofuscinoses of the Haltia‐Santavuori type (both are caused by mutations in palmitoyl‐protein thiosterase gene at 1p32), dentadorubropallidoluysian atrophy (CAG repeats in a gene in 12p13.31) and the mitochondrial syndrome MERRF (tRNA Lys mutation in mitochondrial DNA). In this review, we cover mainly these rapid advances. © 2001 Wiley‐Liss, Inc.
Squirrel monkey chuck call: vocal response to playback chucks based on acoustic structure and affiliative relationship with the caller
Authors: Soltis Joseph , Bernhards Deborah , Donkin Hope , Newman John D. 
Published: October 2002

AbstractAdult female squirrel monkeys (genus Saimiri) that are socially familiar often exchange the chuck vocalization, which differs acoustically across individuals. We used behavioral observations, vocalization playback experiments, and analysis of the acoustic properties of vocalizations to investigate the effect of caller identity and acoustic structure on vocal response to playback chucks in two all‐female social groups (n=10 females). Females were most likely to respond with a chuck to the playback chucks of their closely affiliated partners compared to those of nonaffiliated group members. This shows for the first time that the chuck stimulus alone is sufficient to elicit a chuck response from a female's affiliated partner. Additionally, females responded with a chuck mostly to familiar playback chucks from their own group and least to playbacks of silent controls. Unfamiliar playback chucks from the same species and a different squirrel monkey species elicited chuck responses intermediate between familiar chucks and silent controls. Post‐hoc discriminant function analyses provide preliminary evidence that females are most likely to respond to unfamiliar chucks when those chucks are close in acoustic structure to familiar chucks from their own social group. These results provide a provisional explanation for error in the squirrel monkey signal processing system, in which unfamiliar chucks never heard before nevertheless elicit a chuck response if they are similar in acoustic structure to familiar group chucks. © 2002 Wiley‐Liss, Inc.
Paraneoplastic chorea associated with CRMP‐5 neuronal antibody and lung carcinoma
Authors: Vernino Steven , Tuite Paul , Adler Charles H. , Meschia James F. , Boeve Bradley F. , Boasberg Peter , Parisi Joseph E. , Lennon Vanda A. 
Published: October 2002

AbstractParaneoplastic chorea is described in 16 patients: 11 with limited small‐cell carcinoma, 2 with lung cancer revealed by imaging, 1 with renal cell carcinoma, and 1 with lymphoma. All had CRMP‐5‐IgG; 6 also had ANNA‐1 (anti‐Hu), including 1 without evident cancer. Chorea was the initial and most prominent symptom in 11 patients, asymmetric or unilateral in 5 patients, and part of a multifocal syndrome in 14 patients. Basal ganglia abnormalities were revealed by magnetic resonance imaging and at autopsy (as perivascular inflammation and microglial activation). Four patients improved with chemotherapy, and 2 improved with intravenous methylprednisolone.