bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association study between two variants in the DOPA decarboxylase gene in bipolar and unipolar affective disorder
Authors: Jahnes Esther , Müller Daniel J. , Schulze Thomas G. , Windemuth Christine , Cichon Sven , Ohlraun Stephanie , Fangerau Heiner , Held Tilo , Maier Wolfgang , Propping Peter , Nöthen Markus M. , Rietschel Marcella 
Published: October 2002

AbstractIrregularities of dopaminergic and serotonergic neurotransmission have been implicated in a variety of neuropsychiatric disorders. DOPA decarboxylase (DDC), also known as aromatic L‐amino acid decarboxylase, is an enzyme involved directly in the synthesis of dopamine and serotonin and indirectly in the synthesis of noradrenaline. Therefore, the DDC gene can be considered as a candidate gene for affective disorders. Recently, two novel variants were reported in the DDC gene: a 1‐bp deletion in the promoter and a 4‐bp deletion in the untranslated exon 1. Subsequently, an association case–control study including 112 English patients and 80 Danish patients with bipolar affective disorder (BPAD) revealed a significant association with the 1‐bp deletion. This finding prompted us to analyze whether this effect was also present in a larger and ethnically homogeneous sample of 228 unrelated German patients with BPAD (208 patients with BP I disorder, 20 patients with BP II disorder), 183 unrelated patients with unipolar affective disorder (UPAD), and 234 healthy control subjects. For both BPAD and UPAD we could not detect a genetic association with either variant. Thus, our results do not support an involvement of the 1‐bp or 4‐bp deletion within the DDC gene in the etiology of affective disorders. © 2002 Wiley‐Liss, Inc.
Molecular properties of HLA‐DQ alleles conferring susceptibility to or protection from insulin‐dependent diabetes mellitus: Keys to the fate of islet β‐cells
Authors: Moustakas Antonis K. , Papadopoulos George K. 
Published: October 2002

AbstractThe major histocompatibility complex Class II alleles, HLA‐DQ, and the related HLA‐DR, are the chief genetic elements of human type 1 diabetes. These genes code for polymorphic heterodimeric proteins, whose chief function is to trap peptide antigens in the endosome and present them on the surface of antigen‐presenting cells (dendritic cells, B lymphocytes, monocytes/macrophages) to CD4+T helper cells. A systematic investigation of the molecular properties of HLA‐DQ alleles linked to susceptibility or resistance to type 1 diabetes has shown that these properties segregate along lines of susceptibility or resistance. A correlation of these features with the function of each particular segment of the HLA‐DQ molecule yields interesting insights into the possible pathways leading to type 1 diabetes. There remain, however, areas to be clarified, including mechanisms by which dominant protection is conferred by certain alleles, the interplay between HLA‐DQ and the related locus HLA‐DR, that also shows autoantigen‐specific reactivity, and the cross‐Class help delivered to CD8+T cells, the final effectors in pancreatic β‐cell destruction. Clarification of these issues may lead to ways to prevent diabetes in predisposed individuals already exhibiting the genetic and immunological characteristics, and perhaps a cure in those with the disease, by means of transplantation, and measures for prevention of disease recurrence. © 2002 Wiley‐Liss, Inc.
Leukocyte adhesion deficiency (LAD) type II/carbohydrate deficient glycoprotein (CDG) IIc founder effect and genotype/phenotype correlation
Authors: Etzioni Amos , Sturla Laura , Antonellis Anthony , Green Eric D. , Gershoni‐Baruch Ruth , Berninsone Patricia M. , Hirschberg Carlos B. , Tonetti Michela 
Published: October 2002

AbstractLeukocyte adhesion deficiency (LAD) type II is a rare autosomal recessive syndrome characterized by recurrent infections, typical dysmorphic features, the Bombay blood phenotype and severe growth and psychomotor retardation. It is attributed to a general absence of fucosylated glycans on the cell surface. Three Arab Israeli patients and one Turkish child have been reported so far. The primary defect in a specific GDP‐L‐fucose transporter of the Golgi apparatus has been disclosed recently. All three children reported by us are homozygous for one single founder mutation, different from that reported in the Turkish child. The amount of mRNA of the GDP‐L‐fucose transporter in cells from Arab patients and their parents are comparable to controls. Genotype/phenotype correlation studies show that the two different mutations are distinguished by differences in response to fucose supplementation and in the clinical phenotypes. © 2002 Wiley‐Liss, Inc.
SNPs in the CpG island of NAP1L2: A possible link between DNA methylation and neural tube defects?
Authors: Rogner Ute Christine , Danoy Patrick , Matsuda Fumihiko , Moore Gudrun Elizabeth , Stanier Philip , Avner Philip 
Published: October 2002

AbstractDeletion of the murine X‐linked Nap1l2 gene causes lethality from midgestation onwards. The affected embryos exhibit neural tube defects (NTDs) closely resembling spina bifida and anencephaly in humans. X‐linked familial and spontaneous cases of NTD were analyzed for sequence alterations in the human NAP1L2. No differences were found in the familial cases. However, a number of single nucleotide polymorphisms (SNPs) within the 5′ region of NAP1L2 were identified both in cases of spontaneous NTD and in normal controls. Most of these SNPs lead to the replacement of guanidines or cytosines within a CpG island that is conserved between the human and the mouse promoter regions. Demethylation in vitro activates Nap1l2 transcriptional activity, suggesting the importance of the CpG island in regulating the activity of the Nap1l2/NAP1L2 genes, and the potential importance of the polymorphisms in modifying their transcriptional activity. NAP1L2/Nap1l2 expression may therefore depend on the genetic‐environmental factors that are frequently associated with NTDs. © 2002 Wiley‐Liss, Inc.
Report of a child with aortic aneurysm, orofacial clefting, hemangioma, upper sternal defect, and Marfanoid features: Possible PHACE syndrome
Authors: Slavotinek Anne M. , Dubovsky Elizabeth , Dietz Harry C. , Lacbawan Felicitas 
Published: October 2002

AbstractWe report a female patient who had a scalp hemangioma, a cleft uvula, an upper sternal defect, pectus excavatum, arachnodactyly, pes planus, and joint hypermobility. She had rupture of an aortic aneurysm after minor trauma at 11 years of age. At 17 years of age, elective repair of a dilated, ectatic aorta was complicated by cerebral ischemia. Other vascular abnormalities in the proband included an aneurysm of the left subclavian artery, atresia of the right carotid artery, and calcified cerebral aneurysms. We believe that the proband's physical anomalies are best described by the PHACE (posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities) phenotypic spectrum. This spectrum of physical anomalies also includes sternal clefting and hemagiomas as part of the sternal malformation/vascular dysplasia (SM/VD) association, as found in our patient, and the acronym PHACES has also been used. We consider that the PHACE phenotypic spectrum is likely to be broader than previously recognized and includes orofacial clefting and aortic dilatation and rupture. Our patient also had skeletal anomalies that lead to consideration of Marfan syndrome as a diagnosis. It should be recognized that there is clinical overlap between PHACE syndrome and Marfan syndrome when aortic dilatation is present. We would also like to emphasize the minor nature of the cutaneous findings in our patient despite her severe vascular complications. This is in contrast to previous reports of large or multiple hemangiomas in PHACE syndrome. Published 2002 Wiley‐Liss, Inc.
Balanced X chromosome inactivation patterns in the Rett syndrome brain
Authors: Shahbazian Mona D. , Sun Yaling , Zoghbi Huda Y. 
Published: October 2002

AbstractIn Rett syndrome (RTT), an X‐linked disorder essentially limited to females, neurological development goes awry. Causing this disarray in neuronal function is a mutated form of a protein known as methyl‐CpG‐binding protein 2 (MeCP2). Because the MECP2 gene is subject to X chromosome inactivation (XCI) in females, a number of studies have addressed whether the percentage of cells inactivating the normal vs. mutant chromosome in heterozygous females influences the phenotypic outcome of MECP2 mutations. Because most of these studies measured XCI in peripheral blood, however, interpretation of the results requires the assumption that XCI patterns in blood are representative of those in the brain, the primarily affected tissue. Here, we have analyzed the MECP2 sequence and XCI status in 13 brains of RTT patients. Mutations were identified in nine of the cases, with eight of these representing C to T transitions at CpG dinucleotides, and one being a novel frameshift mutation (765delA). Patterns of XCI were balanced in 10 of 10 cases for which the assay was informative. As previous studies have shown that a majority of RTT patients have balanced XCI patterns in peripheral blood, our results suggest that the pattern in blood is an accurate indicator of XCI patterns in the brain for a majority of cases, but there are some notable exceptions that this study may help explain. Given the correlation between balanced XCI and classic RTT, these results suggest that a certain percentage of neurons expressing the mutant MECP2 gene may be required for RTT to become manifest. © 2002 Wiley‐Liss, Inc.
NovelOCTN2mutations: No genotype–phenotype correlations: Early carnitine therapy prevents cardiomyopathy
Authors: Lamhonwah Anne‐Marie , Olpin Simon E. , Pollitt Rodney J. , Vianey‐Saban Christine , Divry Priscille , Guffon Nathalie , Besley Guy T. N. , Onizuka Russell , De Meirleir Linda J. , Cvitanovic‐Sojat Ljerka , Baric Ivo , Dionisi‐Vici Carlo , Fumic Ksenija , Maradin Miljenka , Tein Ingrid 
Published: October 2002

AbstractPrimary systemic carnitine deficiency or carnitine uptake defect (OMIM 212140) is a potentially lethal, autosomal recessive disorder characterized by progressive infantile‐onset cardiomyopathy, weakness, and recurrent hypoglycemic hypoketotic encephalopathy, which is highly responsive toL‐carnitine therapy. Molecular analysis of theSLC22A5(OCTN2) gene, encoding the high‐affinity carnitine transporter, was done in 11 affected individuals by direct nucleotide sequencing of polymerase chain reaction products from all 10 exons. Carnitine uptake (at Km of 5 μM) in cultured skin fibroblasts ranged from 1% to 20% of normal controls. Eleven mutations (delF23, N32S, and one 11‐bp duplication in exon 1; R169W in exon 3; a donor splice mutation [IVS3+1 G > A] in intron 3; frameshift mutations in exons 5 and 6; Y401X in exon 7; T440M, T468R and S470F in exon 8) are described. There was no correlation between residual uptake and severity of clinical presentation, suggesting that the wide phenotypic variability is likely related to exogenous stressors exacerbating carnitine deficiency. Most importantly, strict compliance with carnitine from birth appears to prevent the phenotype. © 2002 Wiley‐Liss, Inc.
Cytochrome c oxidase deficiency
Authors: Shoubridge Eric A. 
Published: October 2002

AbstractCytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain, catalyzing the transfer of electrons from reduced cytochrome c to molecular oxygen. It is composed of 13 structural subunits, three of which are encoded in mtDNA and form the catalytic core of the enzyme. In addition to these structural subunits, a large number of accessory factors are necessary for the assembly and maintenance of the active holoenzyme complex. Most isolated COX deficiencies are inherited as autosomal recessive disorders; mutations in the mtDNA‐encoded COX subunit genes are relatively rare. These mutations are associated with a wide spectrum of clinical phenotypes ranging from isolated myopathy to multisystem disease, with onset from late childhood to adulthood. Autosomal recessive COX deficiencies generally have a very early age of onset and a fatal outcome. Several clinical presentations have been described including Leigh Syndrome, hypertrophic cardiomyopathy and myopathy, and fatal infantile lactic acidosis. Surprisingly, mutations in the nuclear‐encoded structural COX subunits have not been found in association with any of these phenotypes. Mutations have, however, been identified in several COX assembly factors: SURF1 (Leigh Syndrome), SCO2 (hypertrophic cardiomyopathy), SCO1 (hepatic failure, ketoacidotic coma), and COX10 (encephalopathy, tubulopathy). As all of these assembly factors are ubiquitously expressed, the molecular basis for the different clinical presentations remains unexplained. Although the genetic defects in the majority of patients with COX deficiency are unknown, it is likely that most will be solved in the near future using functional complementation techniques. © 2001 Wiley‐Liss, Inc.
Clinical spectrum and diagnosis of mitochondrial disorders
Authors: Munnich Arnold , Rustin Pierre 
Published: October 2002

AbstractRespiratory chain deficiencies have long been regarded as neuromuscular diseases mostly originating from mutations in the mitochondrial DNA. Actually, oxidative phosphorylation, i.e., adenosine triphosphate (ATP) synthesis‐coupled electron transfer from substrate to oxygen through the respiratory chain, does not only occur in the neuromuscular system. For this reason, a respiratory chain deficiency can theoretically give rise to any symptom, in any organ or tissue, at any age and with any mode of inheritance, owing to the dual genetic origin of respiratory chain enzymes (nuclear DNA and mitochondrial DNA). In recent years, it has become increasingly clear that genetic defects of oxidative phosphorylation account for a large variety of clinical symptoms in both childhood and adulthood. Diagnosis of a respiratory chain deficiency is difficult initially when only one symptom is present, and easier when additional, seemingly unrelated, symptoms are observed. The clinical heterogeneity is echoed by the genetic heterogeneity illustrated by the increasing number of nuclear genes that have been shown to be involved in these diseases. In the absence of clear‐cut genotype‐phenotype correlations and in front of the large number of possibly involved genes, biochemical analyses are still the cornerstone of the diagnosis of this condition. © 2001 Wiley‐Liss, Inc.
Mitochondrial DNA mutations in human disease
Authors: DiMauro Salvatore , Schon Eric A. 
Published: October 2002

AbstractThe small, maternally inherited mitochondrial DNA (mtDNA) has turned out to be a Pandora's box of pathogenic mutations: 13 years into the era of “molecular mitochondrial medicine,” more than 100 pathogenic point mutations and innumerable rearrangements have been associated with a striking variety of multisystemic as well as tissue‐specific human diseases. After reviewing the principles of mitochondrial genetics, we consider disorders due to mutations in genes affecting mitochondrial protein synthesis and disorders due to mutations in protein‐coding genes. In contrast to the remarkable progress in our understanding of etiology, pathogenesis is only partially explained by the rules of mitochondrial genetics and remains largely unclear. We review recent progress in prenatal diagnosis, epidemiology, and in the development of animal models harboring mtDNA mutations. © 2001 Wiley‐Liss, Inc.
Respiratory chain complex I deficiency
Authors: Triepels R.H. , Van Den Heuvel L.P. , Trijbels J.M. , Smeitink J.A. 
Published: October 2002

AbstractOxidative phosphorylation disorders make a contribution of 1 per 10,000 live births in man, of which isolated complex I deficiency is frequently the cause. Complex I, or NADH:ubiquinone oxidoreductase, is the largest multi‐protein enzyme complex of the mitochondrial electron transfer chain. In complex I deficiency, various clinical phenotypes have been recognized, often resulting in multi‐system disorders with a fatal outcome at a young age. Recent advances in complex I deficiency, regarding clinical, biochemical, and molecular aspects are described. However, the genetic causes of about 60% of complex I deficiency remain unclear. As a consequence, further research will be needed to clarify the genetic defects in the remaining cases. Novel strategies in which interesting non‐structural nuclear‐encoded disease‐causing genes may be found, as well as the molecular genetic composition of human complex I, are presented. © 2001 Wiley‐Liss, Inc.
Button osteoma: Its etiology and pathophysiology
Authors: Eshed Vered , Latimer Bruce , Greenwald Charles M. , Jellema Lyman M. , Rothschild Bruce M. , Wish‐Baratz Susanne , Hershkovitz Israel 
Published: October 2002

AbstractThe present study investigates a circumscribed bony overgrowth on the cranial vault, known as button osteoma (BtO) and referred to here as button lesion (BtL). We discuss its anthropological implications. Data on its histology, location, and population distribution (by age, race, and gender) are provided.Microscopically, BtL is composed of well‐organized dense lamellated bone which is poorly vascularized and with very few osteocytes. It forms a dome‐shaped roof over an underlying diploeized area which includes the ectocranial table.The frequency of BtL is similar in modern (37.6%) and archaeological (41.1%) populations, in blacks, whites, males, and females, and correlates with age. It is rare in nonhuman primates. Fifty‐five percent of the human skulls studied by us had BtL only on the parietal, 23.6% on the frontal, and 3.6% on the occipital bones. Fifteen percent had BtL on both the frontal and parietal bones. No lateral preference was found. Most skulls with BtL (64.1%) had only one lesion, 20.4% had two BtL, and 15.4% demonstrated multiple BtL. The average number of button osteomas on an affected skull was 1.97. The frequency of large osteomas (0.5–1.0 cm) was similar in young and old age groups.The demographic characteristics of BtL, mainly its high frequency among ancient and modern populations, its independence of sex and race, its scarcity in other primates, and the fact that its macro‐ and microstruture are indicative of an hamartoma (and not an osteoma or exostosis) suggest an evolutionary background to the phenomenon. Am J Phys Anthropol 118:217–230, 2002. © 2002 Wiley‐Liss, Inc.
The prevalence of narcolepsy among Chinese in Hong Kong
Authors: Wing Yun‐Kwok , Li Raymond Hiu‐Yeung , Lam Ching‐Wan , Ho Crover Kwok‐Wah , Fong Samson Yuk‐Yat , Leung Tony 
Published: October 2002

AbstractNarcolepsy is a lifelong, crippling sleep disorder. Although the discovery of the hypocretin system has been a breakthough in genetics, the epidemiological aspects of narcolepsy remain elusive. Ethnic predisposition was suggested to partially account for the 2,500‐fold difference in the reported prevalence rates of narcolepsy between Japanese (0.59%) and Israeli Jews (0.00023%). We carried out a general population study, conducting a random telephone survey with a structured questionnaire, which included a validated screening instrument (a Chinese version of the Ullanlinna Narcolepsy Scale). It was followed by clinical‐polysomnographic‐HLA confirmation of the subjects determined to be positive for narcolepsy based on the questionnaire. Of 9,851 subjects interviewed, 28 subjects (0.28%, 58% female) were screened positive. Ninety percent had a second detailed interview, 64% had HLA typing, and over half of them had a sleep assessment. Only three subjects were found to have genuine narcolepsy. The most common nonnarcolepsy diagnoses were sleep apnea syndrome and sleep‐wake schedule disorder. The prevalence rate of narcolepsy in Southern (Hong Kong) Chinese was found to be 0.034% (95% confidence interval = 0.010–0.117%). All available narcoleptic subjects were HLA DRB1‐1501 positive and 50% were DQB1‐0602 positive. The prevalence rate of narcolepsy among Chinese is comparable to the rates for other populations in studies with stringent epidemiological designs, suggesting that major cross‐ethnic differences in the prevalence rates of narcolepsy previously reported likely resulted from methodological limitations.
Seizure‐associated hippocampal volume loss: A longitudinal magnetic resonance study of temporal lobe epilepsy
Authors: Briellmann Regula S. , Berkovic Samuel F. , Syngeniotis Ari , King Mark A. , Jackson Graeme D. 
Published: October 2002

AbstractThis longitudinal quantitative magnetic resonance imaging study of 24 patients with mild temporal lobe epilepsy shows an ipsilateral hippocampal volume decrease of 9% (range, −30 to +0.5%; p = 0.002, paired t test) over a period of 3.5 ± 0.7 years. The hippocampal volume loss was correlated to the number of generalized seizures between the scans (p = 0.0007, r = 0.6), suggesting seizure‐associated hippocampal damage.
Electrophysiological findings in X‐linked myopathy with excessive autophagy
Authors: Jääskeläinen Satu K. , Juel Vern C. , Udd Bjarne , Villanova Marcello , Liguori Rocco , Minassian Berge A. , Falck Björn , Niemi Pekka , Kalimo Hannu 
Published: October 2002

AbstractWe report electrophysiological features and magnetic resonance imaging muscle findings in 4 patients and 1 female carrier of X‐linked myopathy with excessive autophagy. Motor units were polyphasic with high mean amplitude and normal duration. The thigh muscles were most severely involved, but myotonic discharges were abundant in both clinically affected and unaffected muscles. Along with the clinicopathological features, these electrophysiological findings distinguish X‐linked myopathy with excessive autophagy from other limb‐girdle myopathies.
Sensory training for patients with focal hand dystonia
Authors: Zeuner Kirsten E. , Bara‐Jimenez William , Noguchi Patricia S. , Goldstein Susanne R. , Dambrosia James M. , Hallett Mark 
Published: October 2002

AbstractSome patients with focal hand dystonia have impaired sensory perception. Abnormal sensory processing may lead to problems with fine motor control. For patients with focal hand dystonia who demonstrate sensory dysfunction, sensory training may reverse sensory impairment and dystonic symptoms. We studied the efficacy of learning to read braille as a method of sensory training for patients with focal hand dystonia. Sensory spatial discrimination was evaluated in 10 patients who had focal hand dystonia and 10 age‐ and gender‐matched controls with a spatial acuity test (JVP domes were used in this test). Clinical dystonia evaluation included the Fahn dystonia scale and time needed to write a standard paragraph. Each individual was trained in braille reading at the grade 1 level for 8 weeks, between 30 and 60 minutes daily, and was monitored closely to ensure that reading was done regularly. Both controls and patients demonstrated improvement on the spatial acuity test. Patients showed a significant mean difference from baseline to 8 weeks on the Fahn dystonia scale. Sixty percent of the patients shortened the time they needed to write a standard paragraph. Improved sensory perception correlated positively with improvement on the Fahn dystonia scale. We conclude that training in braille reading improves deficits in spatial discrimination and decreases disability in patients with focal hand dystonia.