bluuebunny/crossref_metadata_2025_split huggingface dataset:
Follow‐up of a report of a potential linkage for schizophrenia on chromosome 22q12‐q13.1: Part 2
Authors: Pulver Ann E. , Karayiorgou Maria , Lasseter Virginia K. , Wolyniec Paula , Kasch Laura , Antonarakis Stylianos , Housman David , Kazazian Haig H. , Meyers Deborah , Nestadt Gerald , Ott Jurg , Liang Kung‐Yee , Lamacz Malgorzata , Thomas Marion , Childs Barton , Diehl Scott R. , Wang Shengbiao , Murphy Bernadette , Sun Cui‐E , O'Neill F. Anthony , Nie Li , Sham Pak , Burke John , Duke Betty W. , Duke Fiona , Kipps Barbara R. , Bray Joseph , Hunt Wanda , Shinkwin Rosmarie , Nuallain Maurin Ni , Su Ying , Maclean Charles J. , Walsh Dermot , Kendler Kenneth S. , Gill Michael , Vallada Homero , Mant Rebecca , Asherson Philip , Collier David , Parfitt Elizabeth , Roberts Enriquetta , Nanko Shin , Walsh Cathy , Daniels Johanna , Murray Robin , McGuffin Peter , Owen Mike , Laurent Claudine , Dumas Jean‐Baptiste , d'Amato Thierry , Jay Maurice , Martinez Maria , Campion Dominique , Mallet Jacques 
Published: June 2005

AbstractA collaboration involving four groups of investigators (Johns Hopkins University/Massachusetts Institute of Technology; Medical College of Virginia/The Health Research Board, Dublin; Institute of Psychiatry, London/University of Wales, Cardiff; Centre National de la Recherche Scientifique, Paris) was organized to confirm results suggestive of a schizophrenia susceptibility locus on chromosome 22 identified by the JHU/MIT group after a random search of the genome. Diagnostic, laboratory, and analytical reliability exercises were conducted among the groups to ensure uniformity of procedures. Data from genotyping of 3 dinucleotide repeat polymorphisms (at the loci D22S268, IL2RB, D22S307) for a combined replication sample of 256 families, each having 2 or more affected individuals with DNA, were analysed using a complex autosomal dominant model. This study provided no evidence for linkage or heterogeneity for the region 22q12‐q13 under this model. We conclude that if this region confers susceptibility to schizophrenia, it must be in only a small proportion of families. Collaborative efforts to obtain large samples must continue to play an important role in the genetic search for clues to complex psychiatric disorders such as schizophrenia. © 1994 Wiley‐Liss, Inc.
Progress in a genome scan for linkage in schizophrenia in a large Swedish kindred
Authors: Barr C. L. , Kennedy J. L. , Pakstis A. J. , Wetterberg L. , Sjögren B. , Bierut L. , Wadelius C. , Wahlström J. , Martinsson T. , Giuffra L. , Gelernter J. , Hallmayer J. , Moises H. W. , Kurth J. , Cavalli‐Sforza L. L. , Kidd K. K. 
Published: June 2005

AbstractGenetic linkage studies of a kindred from Sweden segregating for schizophrenia have been performed using a genetic model (autosomal dominant, f = 0.72, q = 0.02, phenocopies = 0.001) as described in Kennedy et al., 1988. Analyses of the restriction fragment length polymorphism (RFLP), allele‐specific oligonucleotides (ASO), and short tandem repeat (STR also called microsatellite) data for 180 polymorphisms (individual probe‐enzyme, ASO, or STR systems) at 155 loci have been completed using the MLINK and LIPED programs. Linkage to schizophrenia was excluded, under the given model, at 47 loci; indeterminate lod scores occurred at 108 loci. The total exclusion region across 20 chromosomes is estimated at 330 cM; 211 cM excluded by pairwise analyses and 119 cM previously excluded by multipoint analyses (Kennedy et al., 1989: Schizophr Bull 15:383–391; Moises et al. 1991: Genet Epidemiol 2:99–110; Hallmayer et al., 1992: Arch Gen Psychiatry 49:216–219). © 1994 Wiley‐Liss, Inc.
Analysis of chromosome 22 markers in nine schizophrenia pedigrees
Authors: Coon Hilary , Holik John , Hoff Mark , Reimherr Fred , Wender Paul , Myles‐Worsley Marina , Waldo Merilyne , Freedman Robert , Byerley William 
Published: June 2005

AbstractPrevious results of a genome‐wide survey for schizophrenia susceptibility genes in nine multiplex families indicated a possible region of linkage on chromosome 22. We therefore tested for linkage using ten highly polymorphic chromosome 22 DNA markers. Lod score analyses were suggestive of linkage for several markers on the distal end of the chromosome; however, no lod score exceeded 3 assuming either autosomal dominant or autosomal recessive transmission. The highest lod score was 2.09 (theta = 0.10) for marker D22S276 under autosomal recessive inheritance. Based on simulation analyses, this result is unlikely to represent a false positive. Analyses using information from affected individuals only resulted in reduced lod scores, with a maximum of 1.40 (theta = 0.05) for D22S276 assuming autosomal recessive inheritance. Two nonparametric methods, sib pair analysis and the Affected‐Pedigree‐Member method, also yielded suggestive but inconclusive findings; results were positive, but strict thresholds of significance were not met. Additionally, we tested one candidate gene, the Arylsulfatase A gene, located in the region of 22q13.31‐qter. Results were again inconclusive, though the DNA marker available for this gene was a 2‐allele RFLP with heterozygosity of 0.5, and therefore not maximally informative. Further investigation of this chromosomal region and this and other candidate genes may be warranted. © 1994 Wiley‐Liss, Inc.
Turning point in the design of linkage studies of schizophrenia
Authors: Cloninger C. Robert 
Published: June 2005

AbstractDespite extensive genomic scans, linkage studies of multiplex pedigrees have been unable to produce replicable evidence of genes predisposing to schizophrenia. This indicates that it is unlikely that a single gene accounts for a majority of cases of schizophrenia, even in multiplex pedigrees. It is most likely that schizophrenia is caused by the nonlinear interaction of multiple genetic and environmental factors influencing brain development and function. This conclusion has strong implications for the design of linkage and association studies. Recently designed linkage studies involve several improvements to deal with extensive locus heterogeneity and multiplicative interaction. These improvements include much larger samples of pedigrees, systematic ascertainment and sequential extension rules, and standardized procedures at multiple sites to facilitate collaboration and replication. Future improvements are likely to require advances in the assessment of clinical and neurobiological variability in multiplex pedigrees, more systematic environmental assessment, and advances in analytic methods to deal with multiplicative interaction. Rather than focusing only on schizophrenia as one or more discrete disorders, future linkage efforts should also consider the etiology of individual clinical syndromes or dimensional components of risk that interact to cause the complex pattern of syndromal comorbidity observed within schizophrenics and their families. © 1994 Wiley‐Liss, Inc.
Brain anomalies in velo‐cardio‐facial syndrome
Authors: Mitnick Robin J. , Bello Jacqueline A. , Shprintzen Robert J. 
Published: June 2005

AbstractMagnetic resonance imaging of the brain in 11 consecutively referred patients with velo‐cardio‐facial syndrome (VCF) showed anomalies in nine cases including small vermis, cysts adjacent to the frontal borns, and small posterior fossal. Focal signal hyperintensities in the white matter on long TR images were also noted. The nine patients showed a variety of behavioral abnormalities including mild developmental delay, learning disabilities, and characteristic personality traits typical of this common multiple anomaly syndrome which has been related to a microdeletion at 22q11. Analysis of the behavioral findings showed no specific pattern related to the brain anomalies, and the patients with VCF who did not have detectable brain lesions also had behavioral abnormalities consistent with VCF. The significance of the lesions is not yet known, but the high prevalence of anomalies in this sample suggests that structural brain abnormalities are probably common in VCF. © 1994 Wiley‐Liss, Inc.
Mood disorder service genetic database: Morbidity risks for mood disorders in 3,942 first‐degree relatives of 671 index cases with single depression, recurrent depression, bipolar I, or bipolar II
Authors: Sadovnick A. D. , Remick R. A. , Lam R. , Zis A. P. , Yee I. M. L. , Huggins M. J. , Baird P. A. 
Published: June 2005

AbstractThere is increasing evidence that genetic factors play a role in the etiology of mood disorders. As a result, relatives of affected individuals are more often asking about their own risks to develop a mood disorder.From 1988 to 1990, all consecutive, unrelated inpatients and outpatients (index cases) presenting to the Mood Disorders Service, Department of Psychiatry, University of British Columbia, had detailed family histories taken, thus creating the Mood Disorders Service Genetic Database. Diagnoses for index cases and their first‐degree relatives were made according to Research Diagnostic Criteria and Family History Research Diagnostic Criteria respectively.Morbidity risks for mood disorders were calculated for first‐degree relatives (parents, siblings, children—aged 10 and above) of all index cases with a diagnosis of single depression, recurrent depression, bipolar I, or bipolar II disorder. Morbidity risks were calculated using the maximum likelihood approach. Morbidity risk data are presented according to the sex and diagnosis for the index case in an easy reference format for risk counselling. The risks are presented twice, including and excluding data for “high‐risk” families whose genetic pedigree is suggestive of “autosomal dominant” inheritance. © 1994 Wiley‐Liss, Inc.
Linkage analysis between manic‐depressive illness and 35 classical markers
Authors: Ewald Henrik , Mors Ole , Eiberg Hans 
Published: June 2005

AbstractThe present study used carefully established phenotypes, several methods to reduce misclassification, and conservative genetic parameters. For the 35 markers investigated no evidence of linkage to manic‐depressive illness was found, especially not to the markers on chromosomes 4q, 9q, and 19, which earlier has been suggested as possibly being linked to subtypes of manic‐depressive illness. Close linkage to FY and SS (GYPB) was excluded for all chosen phenotypic models and to ACP1 and ADA for broader phenotypic models. © 1994 Wiley‐Liss, Inc.
Genetic linkage mapping for a susceptibility locus to bipolar illness: Chromosomes 2,3,4,7,9,10p,11p,22, and Xpter
Authors: Detera‐Wadleigh Sevilla D. , Hsieh Wang‐Ting , Berrettini Wade H. , Goldin Lynn R. , Rollins Denise Y. , Muniec David , Grewal Raji , Guroff Juliet J. , Turner Gordon , Coffman Diane , Barrick J. , Mills Kate , Murray Jeffrey , Donohue Susan J. , Klein David C. , Sanders Jason , Nurnberger John I. , Gershon Elliot S. 
Published: June 2005

AbstractWe are conducting a genome search for a predisposing locus to bipolar (manicdepressive) illness by genotyping 21 moderate‐sized pedigrees. We report linkage data derived from screening marker loci on chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and the pseudoautosomal region at Xpter. To analyze for linkage, two‐point marker to illness lod scores were calculated under a dominant model with either 85% or 50% maximum penetrance and a recessive model with 85% maximum penetrance, and two affection status models. Under the dominant high penetrance model the cumulative lod scores in the pedigree series were less than −2 at Θ = 0.01 in 134 of 142 loci examined, indicating that if the disease is genetically homogeneous linkage could be excluded in these marker regions. Similar results were obtained using the other genetic models. Heterogeneity analysis was conducted when indicated, but no evidence for linkage was found. In the course of mapping we found a positive total lod score greater than +3 at the D7S78 locus at Θ = 0.01 under a dominant, 50% penetrance model. The lod scores for additional markers within the D7S78 region failed to support the initial finding, implying that this was a spurious positive. Analysis with affected pedigree member method for COL1A2 and D7S78 showed no significance for linkage but for PLANH1, at the weighting functions f(p) = 1 and f(p) = 1/sqrt(p) borderline P values of 0.036 and 0.047 were obtained. We also detected new polymorphisms at the mineralocorticoid receptor (MLR) and calmodulin II (CALMII) genes. These genes were genetically mapped and under affection status model 2 and a dominant, high penetrance mode of transmission the lod scores of < −2 at Θ = 0.01 were found. © 1994 Wiley‐Liss, Inc.
Role of genetic factors in human sexual behavior based on studies of tourette syndrome and ADHD probands and their relatives
Authors: Comings David E. 
Published: June 2005

AbstractMost significant variations in the expression of human sexuality are considered to be the result of learned behavior or psychological problems. Tourette syndrome (TS) is a common, hereditary tic and disinhibition disorder sometimes associated with compulsive use of obscene words (coprolalia) and previously reported to be occasionally associated with exhibitionism. To further explore the relationship between the Gts genes and sexual behavior, questions concerning a wide range of such behaviors were administered to 1,040 subjects, 14 years of age or older, consisting of 358 TS probands, 101 non‐proband relatives with TS, 359 non‐TS first degree relatives, 79 attention deficit hyperactivity disorder (ADHD) probands, 70 unaffected relatives of the ADHD probands, and 73 controls. The behaviors included magnitude of sex drive, sex orientation, exhibitionism, transvestitism, transsexualism, sadism, masochism, pedophilia, fetishism, aversion to being touched, and aversion to sex. While most of these behaviors occurred in a distinct minority of TS subjects, there was a significant positive correlation between each behavior examined and the degree of genetic loading for the Gts gene(s). The nature of these behaviors and their association with TS suggests many are variants of obsessive‐compulsive disorder. Studies in animals indicate that changes in serotonin and dopamine play a significant role in the sexual behavior and many lines of evidence are consistent with the hypothesis that TS is due to genetic changes in serotoun and dopamine metabolism. These studies suggest that genetic factors play a much greater role in a wide range of forms of sexual expression than previously thought. © 1994 Wiley‐Liss, Inc.
Clinical and biochemical analysis of two families with type I and type II mannosidosis
Authors: Bennet J. K. , Dembure P. P. , Elsas L. J. 
Published: June 2005

AbstractWe report on two unrelated patients with different presentations of mannosidosis. One patient was affected in early childhood with a severe phenotype characteristic of type I mannosidosis. The other was diagnosed with type II mannosidosis only after the onset of progressive neurologic deterioration in late adulthood. Both were detected by non‐invasive urinary screening of oligosaccharides. Lymphoblasts transformed from both patients' blood cells had markedly reduced lysosomal α‐mannosidase activity. Kinetic analyses showed that α‐mannosidase from the type I patient had a 400‐fold reduction in affinity while that from the type II patient was reduced 40‐fold. Lymphoblasts from all 4 parents had reduced α‐mannosidase activity, but there were overlapping activities among these type I and type II obligate heterozygotes. We conclude that screening urinary oligosaccharides will detect mannosidosis over a wide range of phenotypes, that lymphoblasts transformed from affected heterozygotes have decreased enzymatic activity, and that the severity of clinical expression is related to the degree of enzyme impairment. © 1995 Wiley‐Liss, Inc.
Duplication 3q syndrome: Molecular delineation of the critical region
Authors: Aqua Mfon S. , Rizzu Patrizia , Lindsay Elizabeth A. , Shaffer Lisa G. , Zackai Elaine H. , Overhauser Joan , Baldini Antonio 
Published: June 2005

AbstractThe phenotype of dup(3q) syndrome partially overlaps with Brachmann‐de Lange phenotype. Convulsions and eye, palate renal, and cardiac anomalies are more frequent in dup(3q) syndrome, while limb deficiencies, hirsutism, and synophrys are more characteristic of Brachmann‐de Lange syndrome. Whether the two syndromes have a biological relationship has yet to be demonstrated. Using two patient translocation cell lines, each involving distal 3q, we have narrowed the critical region of the dup(3q) syndrome to the interval 3q26.31–q27.3 and initiated its molecular characterization. We have mapped in this region 6 cosmid clones spanning approximately 3–5 Mb. The critical region appears to overlap with the region where a balanced translocation was found in a Brachmann‐de Lange patient. This work provides the mapping framework for finer molecular analysis of dup(3q) syndrome. © 1995 Wiley‐Liss, Inc.
“Balanced” karyotypes in six abnormal offspring of balanced reciprocal translocation normal carrier parents
Authors: Wenger Sharon L. , Steele Mark W. , Boone Leslie Y. , Lenkey Sharen G. , Cummins James H. , Chen Xiao‐Qing 
Published: June 2005

AbstractAmong 6800 consecutive blood samples studied for clinical cytogenetic diagnosis, we identified 30 families in which one parent of the proband had a balanced reciprocal autosomal translocation (excluding Robertsonian rearrangements). Twentyeight of the 30 families had a malformed and/or mentally retarded proband: 19 with an unbalanced derived chromosome, 3 with abnormalities involving chromosomes other than those in the translocation, 5 with a “balanced” reciprocal translocation, and 1 with a normal karyotype. We hypothesize that the latter 6 affected probands with “balanced” karyotypes could be abnormal due to submicroscopic deletions and duplications as was originally suggested by Jacobs [1984]. Particularly in these 6 families, 83% of translocation breakpoints were associated with fragile sites, more than expected by chance (P < 0.025). This supports the report of an association between fragile sites and constitutional chromosome breakpoints by Hecht and Hecht [1984]. To explain these findings, we propose that autosomal fragile sites are unstable areas which predispose to breaks and unequal crossing over near the fragile site breakpoints creating minute duplications and deletions. Consequently, newborn infants inheriting a seemingly “balanced” karyotype from a normal parent with a balanced reciprocal translocation may still be at an increased risk of being malformed and/or developmentally delayed because of submicroscopic chromosomal imbalances. © 1995 Wiley‐Liss, Inc.
Dandy‐Walker malformation in the Meckel syndrome
Authors: Summers Michael C. , Donnenfeld Alan E. 
Published: June 2005

AbstractThe Meckel syndrome (MS) is an autosomal recessive disorder classically defined by the triad of occipital encephalocele, multicystic kidneys, and polydactyly. Here we describe 3 sibs with varying manifestations of MS. The propositus had isolated cystic renal disease. The other sibs were both prenatally diagnosed with renal disease, polydactyly, and the Dandy‐Walker malformation, an unusual central nervous system defect in MS. These findings are discussed in the context of the phenotypic expression of MS and the nosology of this disorder and the cerebro‐reno‐digital (Meckel‐like) syndromes. © 1995 Wiley‐Liss, Inc.
Expression of SRY transcripts in preimplantation human embryos
Authors: Fiddler Morris , Abdel‐Rahman Burae , Rappolee Daniel A. , Pergament Eugene 
Published: June 2005

AbstractWe have examined the expression of SRY mRNA in individual in vitro fertilized preimplantation human embryos; because of ethical constraints, these studies were confined to embryos with one and three pronuclei. Using a sensitive reverse transcriptase‐polymerase chain reaction (RTPCR) assay, we observed SRY mRNA at the one‐cell through the blastula stages but not in spermatozoa. These results indicate that the de novo transcription of this sex‐specific gene occurs at a developmental time considerably earlier than that of gonadal differentiation. Our results also indicate that in vitro fertilized embryos with one pronucleus are likely to be diploid. © 1995 Wiley‐Liss, Inc.
Hereditary congenital posterior dislocation of radial heads
Authors: Reichenbach Herbert , Hörmann Dieter , Theile Herbert 
Published: June 2005

AbstractWe report on 4 patients with congenital posterior dislocation of radial heads in 3 generations of a family. Radiographs of the elbow joints of 3 individuals are presented. All affected subjects have mild limitation of extension and a strong restriction of rotation in the elbows. Comparison with previously described patients shows similarities in the X‐ray findings. Congenital posterior dislocation of the radial head can be unilateral or bilateral. This malformation is also found in patients with antecubital pterygium or nailpatella syndrome. This family confirms the autosomal dominant inheritance of congenital posterior dislocation of radial heads. © 1995 Wiley‐Liss, Inc.
Androgen receptor gene (CAG)n repeat analysis in the differential diagnosis between Kennedy disease and other motoneuron disorders
Authors: Ferlini A. , Patrosso M. C. , Guidetti D. , Merlini L. , Uncini A. , Ragno M. , Plasmati R. , Fini S. , Repetto M. , Vezzoni P. , Forabosco A. 
Published: June 2005

AbstractAn increase in the number of (CAG)n repeats in the first coding exon of the androgen receptor (AR) gene has been strongly associated with Kennedy disease (KD) (spinal and bulbar muscular atrophy). This is an X‐linked hereditary disorder characterized by motoneuron degeneration occurring in adults together with gynecomastia and hyperestrogenemia. We have performed AR gene molecular analysis in several members of a large family with KD as well as in 25 sporadic patients suffering from heterogeneous motoneuron disease (MND). An increase in the length of the (CAG)n repeats was detected, as expected, in all the affected males and in obligatory carrier females, some of which had minor signs of lower motoneuron involvement. There was only one possible exception, one young male with initial signs of the disease, who had an apparent normal length allele. An increased pathological allele was also found in 3 patients with MND. This indicates that the analysis of (CAG)n repeats of the AR gene plays a role in the differential diagnosis of this heterogeneous group of neurological diseases. © 1995 Wiley‐Liss, Inc.
Deletion of chromosome 2q24‐q31 causes characteristic digital anomalies: Case report and review
Authors: Boles Richard G. , Pober Barbara R. , Gibson Lisa H. , Willis Charla R. , McGrath James , Roberts Drucilla J. , Yang‐Feng Teresa L. 
Published: June 2005

AbstractWe describe a newborn boy with multiple anomalies, including bilateral split foot and an interstitial deletion of chromosome 2 (q24.2‐q31.1). Four additional cases in 2 families involving similar deletions have been reported. Bilateral digital anomalies of hands and feet were seen in all 5 cases, including a wide cleft between the first and second toes, wide halluces, brachysyndactyly of the toes, and camptodactyly of the fingers. Other common manifestations have included postnatal growth and mental retardation, microcephaly, down‐slanting palpebral fissures, micrognathia, and apparently low‐set ears. Bilateral digital anomalies were reported in 22 of 24 cases with deletions including at least part of region 2q24‐q31. Digital anomalies were not prevalent in 18 patients with deletions of chromosome 2q not overlapping 2q24‐q31. 2q31.1 appears to be the common deleted segment in all cases with significant digital anomalies, which implies the existence of one or more genes involved in distal limb morphogenesis in this region. HOXD13 and EVX2, located in the proximity of 2q31, were not deleted in our patient by Southern analysis.Bilateral digital malformations of the hands and feet associated with other anomalies should be evaluated by chromosome analysis focused at the 2q24‐q31 region. © 1995 Wiley‐Liss, Inc.