摘要:

AbstractAn association has been observed in several independent data sets between late onset Alzheimer's Disease (AD) and the APOE locus on chromosome 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at‐risk siblings of the FHP group we found an excess of the ϵ4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and non‐stringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease free survival suggested that APOE genotype contributes a small fraction of the total variance indicating that the APOE locus is a poor predictor of disease free survival age within late onset families. One explanation for the age dependent association reported by other groups, and our results, is that the APOE locus enhances the rate of progression of the disease process in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause the disease. We suggest this hypothesis is compatible with the current literature regarding APOE and AD. © 1995 Wiley‐Li

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600102

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe diagnostic classification of schizoaffective psychoses has varied much since Kasanin introduced the concept in 1933. The various classifications have agreed that schizoaffective psychoses present a combination of schizophreniform and affective symptoms, but the diagnostic criteria differ as to the number, quality, and time sequence of the symptoms even in recent classifications like RDC, DSM‐III‐R, and ICD‐10. The classifications are syndromatical, and the etiology of the schizoaffective psychoses is still undetermined apart from evidence for a strong genetic factor. Results from family, twin, and adoption studies are divergent, but all the same, support a separate classification of broadly defined schizoaffective psychoses as possibly being phenotypical variations or expressions of genetic interforms between schizophrenia and affective psychoses. © 1995 Wiley‐L

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600103

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

年代:1995

数据来源: WILEY

摘要:

AbstractAlzheimer's disease (AD) is a progressive, degenerative neurological disorder of the central nervous system. AD is the fourth leading cause of death in elderly persons 65 years or older in Western industrialized societies. The etiology of AD is unknown, but clinical, pathological, epidemiological, and molecular investigations suggest it is etiologically heterogeneous. Mutations in the amyloid protein are rare and segregate with the disease in a few early‐onset familial AD (FAD) families. Similarities between AD and the unconventional viral (UCV) diseases, and between the amyloid and prion proteins, implicate the human prion protein gene (PRNP) as another candidate gene. Single strand conformation polymorphism (SSCP) analysis was used to screen for mutations at this locus in 82 AD patients from 54 families (30 FAD), vs. 39 age‐matched controls. A 24‐bp deletion around codon 68 that codes for one of five Gly‐Pro rich octarepeats was identified in two affected sibs and one offspring of one late‐onset FAD family. Two other affected sibs, three unaffected sibs, and three offspring from this family, in addition to one sporadic AD patient and three age‐matched controls, were heterozygous for another octarepeat deletion located around codon 82. Two of the four affected sibs had features of PD, including one who was autopsy‐verified AD and PD. Although these deletions were found infrequently in other AD patients and controls, they appear to be a rare polymorphism that is segregating in this FAD family. It does not appear that mutations at the PRNP locus are frequently associated with AD in this population. © 1995 W

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600104

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe purpose of this study is to test the hypothesis that major affective and/or anxiety disorders are increased among relatives of autistic probands compared with controls. Among 36 families with an autistic child, 23 (64%) have a first degree relative diagnosed with major depressive disorder and 14 (39%) have a first degree relative diagnosed with social phobia. These rates are significantly greater than the 19% and 5%, respectively, found among 21 families with a child having a genetic condition, tuberous sclerosis complex, or a seizure disorder but no autism. The frequency of major depression among the 96 first degree relatives of autistic probands is 37.5% compared with 11.1% found among 45 relatives of control probands. The frequency of social phobia, 20.2%, is approximately 10 times more common than that found among the relatives of the control probands (2.4%). Elevated rates of both major depression and social phobia are found among parents and siblings in the families with an autistic child. Furthermore, 64% of parents affected with a major depression had the onset of the first depressive episode prior to the birth of the autistic child and all parents with social phobia had the onset of condition prior to the birth of the autistic child.Family patterns differ depending on the intellectual level of the autistic child; specifically, social phobia is significantly greater among the first degree relatives of nonretarded autistic probands than among relatives of individuals with autism and comorbid mental retardation. Whether this familial association of autism, major mood disorders, and social phobia reflects shared genetic underpinnings requires further research. © 1995 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600105

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe had previously reported that patients affected with BMD have a significantly reduced reproductive performance (f = 0.12) as compared to male LGMD patients of similar age and physical impairment (f = 0.98). In the present study parameters such as the socio‐economic level, as well as psycho‐social, intellectual, and psychiatric functionings could not explain the low fitness of BMD patients. The effect of genetic counseling, a greater difficulty in coping with the disease, and relating to women and/or a potential malfunction of reproductive physiology are discussed as possible causes. © 1995 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600106

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

年代:1995

数据来源: WILEY

摘要:

AbstractThere are some indications that Becker muscular dystrophy (BMD) might be related to mental disorders and mental retardation (MR). To investigate this question, we made a standardized psychiatric and intellectual level assessment of 22 BMD patients in comparison with 22 limb‐girdle muscular dystrophy (LGMD) patients. There were not significant differences between the two groups. Twelve patients (54.5%) in each group received at least one lifetime psychiatric diagnosis, the most frequent being depressive disorders. The intelligence quotient means for BMD was 85.9 and 87.8 for LGMD. There was one case of mild MR among BMD patients and two cases among LGMD patients. © 1995 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600107

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

年代:1995

数据来源: WILEY

摘要:

AbstractSpeech/language disorders are common in the fragile X syndrome. [Howard‐Peebles, 1979: Am J Hom Genet 31:214–222; Renier et al., 1983: J Ment Defic Res 27:51–59; Sparks, 1984: Birth Defects and Speech‐Language Disorders, pp. 39–43; Hanson et al., 1986: Am J Med Genet 23:195–206]. Verbal paraphasias have been considered a rare feature and word‐finding difficulties have seldom been reported. Here we report on ten Brazilian patients who were evaluated for speech/language disturbances and found that word‐finding difficulties were present in 50% of the cases, which is a slightly higher frequency than that of clear dyspraxia. We suggest, therefore, that word‐finding difficulties and verbal dyspraxia can be a common feature within the spectrum of this syndrome. Additional speech findings are discussed. © 19

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600108

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

年代:1995

数据来源: WILEY

摘要:

AbstractEarly onset familial Alzheimer's disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the β‐amyloid precursor protein (βAPP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with βAPP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val → Ile) or a valine to glycine (Val → Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the βAPP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the βAPP717 Val → Ile and βAPP717 Val → Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or βAPP codon 717 mutated families except mean age of onset. © 199

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600109

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

年代:1995

数据来源: WILEY

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600116

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

年代:1995

数据来源: WILEY

摘要:

AbstractOver a 3.5 year period of time, 345 patients hospitalized for psychiatric problems were evaluated cytogenetically. The patient population included 76% males and 94% children with a mean age of 12 years. The criteria for testing was an undiagnosed etiology for mental retardation and/or autism. Cytogenetic studies identified 11, or 3%, with abnormal karyotypes, including 4 fragile X positive individuals (2 males, 2 females), and 8 with chromosomal aneuploidy, rearrangements, or deletions. While individuals with chromosomal abnormalities do not demonstrate specific behavioral, psychiatric, or developmental problems relative to other psychiatric patients, our results demonstrate the need for an increased awareness to order chromosomal analysis and fragile X testing in those individuals who have combinations of behavioral/psychiatric, learning, communication, or cognitive disturbance. © 1995 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600110

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

年代:1995

数据来源: WILEY