摘要:

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, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe used 10 highly informative DNA polymorphic markers and genetic linkage analysis to examine whether a gene locus predisposing to schizophrenia is located on chromosome 22, in 105 families with schizophrenia and schizoaffective disorder. The LOD score method, including analysis for heterogeneity, provided no conclusive evidence of linkage under a dominant, recessive, or penetrance free model of inheritance. Affected sib‐pair analysis was inconclusive. Affected pedigree member analysis gave only suggestive evidence for linkage. Multipoint APM analysis, using 4 adjacent loci including D22S281 and IL2RB, a region of interest from the APM analysis, gave non‐significant results for the three different weighting functions. © 1994 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

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‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractPsychiatric disorders have been reported in over 10% of patients with velo‐cardio‐facial syndrome (VCFS) in long‐term follow‐up. To further explore the behavioral and psychiatric findings associated with VCFS in adulthood, detailed clinical histories of two patients—one with VCFS who developed a psychotic illness, and one with schizophrenia who was found to have dysmorphological features associated with VCFS—are described in the current report. The observed overlap of physical and psychiatric symptoms in these two patients suggests that VCFS and psychotic disorders may share a pathogenetic mechanism. This could be consistent with a contiguous gene model for VCFS and psychosis, suggesting chromosome 22q11 as a possible candidate region for genetic studies of schizophrenia. © 1994 Wil

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractMarkers for X chromosome loci were used in linkage studies of a large group of small families (n = 126) with at least two schizophrenic members in one sibship. Based on the hypothesis that a gene for schizophrenia could be X‐Y linked, with homologous loci on both X and Y, our analyses included all families regardless of the pattern of familial inheritance. Lod scores were computed with both standard X‐linked and a novel X‐Y model, and sibpair analyses were performed for all markers examining the sharing of maternal alleles. Small positive lod scores were obtained for loci pericentromeric, from Xp11.4 to Xq12. Lod scores were also computed separately in families selected for evidence of maternal inheritance and absence of male to male transmission of psychosis. The lod score for linkage to the locus DXS7 reached a maximum of 1.83 at 0.08% recombination, assuming dominant inheritance on the X chromosome in these families (n = 34). Further investigation of the X‐Y homologous gene hypothesis focussing on this region is warranted. © 1994 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractTwo separate groups of dyslexia families were ascertained through probands attending special schools for dyslexic students. An additional control group of families was ascertained through randomly selected students attending public schools. The 3 groups were interviewed by questionnaire about the family's demographic characteristics, and about the incidence of reading and spelling disorders in all first and second order relatives. One group of dyslexia families was also examined by standardized intelligence and academic achievement tests. Developmental dyslexia was found to aggregate in families; there were 4–5 times as many affected males as females among clinically identified students attending the special schools, but the sex ratio of affected relatives after probands had been excluded was approximately 1.4 males for every female. Sibs were at greater risk for reading difficulties when one parent was affected than when neither parent was affected. Sibs were also at greater risk for academic difficulties, andaffectedsibs were more severely impaired, when the father rather than the mother was the affected parent. In dyslexia families with 2 affected parents, the sibs were at greater risk, and the affected sibs were more severely impaired, than in families where only one parent was affected. Moreover, in families with 2 affected parents, both of the parents were more severely impaired in reading and spelling than parents of the same sex in families with one affected parent. Some indirect evidence is presented that assortative mating may codetermine patterns of affectedness in dyslexia families. © 1994 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

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

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractOver the last 20 years several pedigrees have been reported which are suggestive of linkage between susceptibility to bipolar disorder and markers on chromosome Xq28. Other workers have failed to replicate these reports and the methodology of the positive reports has been criticised. Recently there have been several reports of an association between fragile X (FRA(X)) and affective disorder within families and in unrelated individuals compared with controls. Such reports could be consistent with the Xq28 marker reports because FRA(X) maps to Xq27.3. We report a study at the FRA(X) CGG repeat locus in 79 unrelated Caucasian bipolar probands without fragile X syndrome and 77 unrelated controls. We found no evidence that variation at this locus confers susceptibility to bipolar disorder. © 1994 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

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‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractPrevious population studies of hearing loss have been limited to children with moderate to profound impairment, and have reported that heritability accounts for at least 50% of congenital or early‐onset cases. The present study was designed to assess genetic factors associated with late‐onset hearing impairment in an adult population. A brief family history and audiologic questionnaire was sent to approximately 11,200 members of the consumer organization, Self Help for the Hard of Hearing, Inc., and 4,039 questionnaires were returned. All respondents reported having at least one previous audiologic exam. Reported data were verified against audiograms when available. Regardless of thereportedcauses, 49% of early‐onset cases (⩽20 years of age) had one or two parent(s) with some form of hearing loss compared with 62% in later‐onset cases. As expected, mean age at onset was substantially younger for cases with positive family histories than cases with negative family histories. Results from nuclear segregation analysis showed that fully recessive and dominant models failed to explain the early‐ or late‐onset hearing loss data.In this nationwide survey, the large proportion of cases with positive family histories clearly indicates the importance of genetic factors in adult‐onset forms of hearing loss. Comparison with younger‐onset cases will permit further delineation of differences in inheritance patterns. This study should identify more homogeneous groups of adult‐onset families for further genetic study, and provide empiric information for use in genetic counselling. ©

ISSN:0148-7299    

DOI:10.1002/ajmg.1320540211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY