摘要:

AbstractObsessive compulsive disorder (OCD) often coexists with major depression (MD), with rates varying from 35 to 75%. The nature of the depressive symptomatology can be investigated by familial aggregation analysis, assuming that the disorder which occurs first is the one showing greater genetic liability and should have higher familial concentration. Therefore, the aim of our study was to assess the familial loading for OCD and mood disorders in the families of OCD patients with different chronology of onset for the mood disorder, to evaluate how the familial pattern of the diseases differs with different temporal sequences in which the two syndromes occur. A total of 172 OCD patients entered the study; 112 were pure OCD probands, 12 were unable to separate the onset of the two syndromes, 11 had prior mood disorder, and 37 of them had experienced their first depressive episodes after the onset of OCD.Information about the family history was collected by means of the Family History‐Research Diagnostic Criteria (FH‐RDC) and by directly interviewing at least 2 relatives per family. Morbidity risks for OCD indicate a familial concentration of the disorder in all groups, except the MD/OCD group. We found the highest rate of relatives affected by mood disorders in the families of patients with first onset of MD (28.8%), whereas in the other 3 groups MRs were much lower. These results suggest the affective nature of OCD patients who experienced first onset of MD. Thus, the chronology of onset seems to identify 2 different typologies of familial distribution. © 1995 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600602

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

年代:1995

数据来源: WILEY

摘要:

AbstractTo understand the implications of suboptimal gene expression in fragile X syndrome [fra(X)], we sought to define the central nervous abnormalities in fra(X) syndrome to determine if abnormalities in specific brain regions or networks might explain the cognitive and behavioral abnormalities in this syndrome. Cranial and ventricular volumes were measured with quantitative computed tomography (CT), regional cerebral metabolic rates for glucose (rCMRglc) were measured with [18‐F]‐2‐fluoro‐2‐deoxy‐D‐glucose (18FDG), and patterns of cognition were determined with neuropsychological testing in ten healthy, male patients with karyotypically proven fra(X) syndrome (age range 20–30 yr). Controls for the CT studies were 20 healthy males (age range 21–37 yr), controls for the PET studies were 9 healthy males (age range 22–31 yr), and controls for the neuropsychological tests were 10 young adult, male Down syndrome (DS) subjects (age range 22–31 yr). The mean mental age of the fra(X) syndrome group was 5.3 yr (range 3.5–7.5 yr; Stanford‐Binet Intelligence Scale). Despite comparable levels of mental retardation, the fra(X) subjects showed poorer attention/short term memory in comparison to the DS group. Further, the fra(X) subjects showed a relative strength in verbal compared to visuospatial attention/short term memory. As measured with quantitative CT, 8 fra(X) subjects had a significant (P<0.05) 12% greater intracranial volume (1,410 ± 86 cm3) as compared to controls (1,254 ± 122 cm3). Volumes of the right and left lateral ventricles and the third ventricle did not differ between groups. Seven of eight patients had greater right lateral ventricle volumes than left, as opposed to 9 out of 20 controls (P<0.05). Global gray matter CMR‐glc in nine fra(X) patients was 9.79 ± 1.28 mg/100 g/minute and did not differ from 8.84 ± 1.31 mg/100 g/minute in the controls. R/L asymmetry in metabolism of the superior parietal lobe was significantly higher in the patients than controls. A preliminary principal component analysis of metabolic data showed that the fra(X) subjects tended to form a separate subgroup that is characterized by relative elevation of normalized metabolism in the lenticular nucleus, thalamus, and premotor regions. Further, a discriminant function, that reflected rCMRglc interactions of the right lenticular and left premotor regions, distinguished the fra(X) subjects from controls. These regions are part of a major group of functionally and anatomically related brain regions and appear disturbed as well in autism with which fra(X) has distinct behavioral similarities. These results show a cognitive profile in fra(X) syndrome that is distinct from that of Down syndrome, that the larger brains in fragile X syndrome are not accompanied by generalized cerebral cortical atrophy or hypoplasia, and that distinctive alterations in resting regional glucose metabolism, measured with 18 FDG and PET, occur in fra(X) syndrome. © 1995 Wiley‐Liss, Inc.This article is a U.S. Government work and, as such, is in the public doma

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600603

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe motor control of bimanual coordination and motor speech was compared between first degree relatives from families with at least 2 dyslexic family members, and families where probands were the only affected family members. Half of affected relatives had motor coordination deficits; and they came from families in which probands also showed impaired motor coordination. By contrast, affected relatives without motor deficits came from dyslexia families where probands did not have motor deficits. Motor coordination deficits were more common and more severe among affected offspring in families where both parents were affected than among affected offspring in families where only one parent was affected. However, motor coordination deficits were also more common and more severe in affectedparentswhen both parents were affected than among affected parents in families where only one parent was affected.We conclude that impaired temporal resolution in motor action identifies a behavioral phenotype in some subtypes of developmental dyslexia. The observed pattern of transmission for motor deficits and reading impairment in about half of dyslexia families was most congruent with a genetic model of dyslexia in which 2 codominant major genes cosegregate in dyslexia pedigrees where the proband is also motorically impaired. © 1995 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600604

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

年代:1995

数据来源: WILEY

摘要:

AbstractAlthough schizophrenia clusters in families, it is not inherited in Mendelian fashion. This suggests that there may be alternative phenotypic expressions of genes that convey risk for schizophrenia, such as more elementary physiological or biochemical defects. One proposed phenotype is impaired inhibitory gating of the auditory evoked potential to repeated stimuli. Normally, the amplitude of the P50 response to the second stimulus is significantly less than the response to the first, but this gating of response is generally impaired in schizophrenia. Clinically unaffected individuals within a pedigree who have both an ancestral and descendant history of schizophrenia may be useful for studying whether this physiological defect is a possible alternative phenotype. We have studied inhibitory gating of the auditory P50 response to pairs of auditory stimuli in 17 nuclear families. In 11, there was one parent who had another relative with a chronic psychotic illness, in addition to the schizophrenic proband. All of the parents with family histories of schizophrenia had gating of the P50 response similar to their schizophrenia offspring, whereas only 7% of the parents without family history had gating of the P50 response in the abnormal range. These results support loss of gating of the auditory P50 wave as an inherited deficit related to schizophrenia and suggest that studies of parents may help elucidate the neurobiological expression of genes that convey risk for schizophrenia. © 1995 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600605

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

年代:1995

数据来源: WILEY

摘要:

AbstractFamilial amyloidotic polyneuropathy (FAP‐type I) was first described in Portugal by Andrade in 1952, a time when 54 among 64 patients (belonging to 25 families) originated from Póvoa do Varzim or its surrounding districts. Since then, a total of 1,233 patients, belonging to 489 pedigrees (so far unrelated), have been diagnosed at Centro de Estudos de Paramiloidose, Porto, Portugal. Although age‐of‐onset showed a wide range (17 to 78 years), 87% of these 1,233 patients developed symptoms before 40 years of age (mean 33.5, SD 9.4 years).Among all patients, 432 belong to 140 families originating from the area of Póvoa do Varzim/Vila do Conde, 330 of whom lived in that area at the time of diagnosis; age‐of‐onset was, on average, lower than in the overall group of patients (mean 31.1, SD 6.7 years), and no patient had onset after 57 years (versus 3.3% in the global sample). As in previous studies, women were found to have a later onset (33.7) than men (29.0) years. In 1991, the crude prevalence rate was 90.3 × 10−5(one in every 1,108 inhabitants), and the frequency of gene carriers was estimated to be 186 × 10−5(one in every 538); about 48.4% of these carriers had manifested symptoms by 1991.Female patients had a significantly higher number of children (mean 3.7, SD 2.6) than male patients (mean 2.7, SD 2.1) and the length of their reproductive period (mean 8.4, SD 5.8 yr) was also greater than for men (mean 5.6, SD 4.4 yr). Altogether, the 122 patients who ever reproduced contributed 457 children to the next generation, a mean fertility of 3.7. Further studies using a control groups may answer the question of whether this is the result of a specific high fertility of these patients or just their belonging to a population in natural expansion. © 19

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600606

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe 11q21‐22 region is of interest for schizophrenia because several candidate genes are located in this section of the genome. The 11q21‐22 region, including DRD2, was surveyed by linkage analysis in a sample (N = 242) made of four large multigenerational pedigrees densely affected by schizophrenia (SZ) and eight others by bipolar disorder (BP). These pedigrees were ascertained in a large area of Eastern Quebec and Northern New Brunswick and are still being extended. Family members were administered a “consensus best‐estimate diagnosis procedure” (DSM‐III‐R criteria) blind to probands and relatives' diagnosis and to pedigree assignment (SZ or BP). For linkage analysis, 11 microsatellite polymorphism (CA repeat) markers, located at 11q21‐22, and comprising DRD2, were genotyped. Results show no evidence of a major gene for schizophrenia. However, a maximum lod score of 3.41 at the D11S35 locus was observed in an affected‐only analysis of one large SZ family, pedigree 255. Whether or not the positive linkage trend in pedigree 255 reflects a true linkage for a small proportion of SZ needs to be confirmed through the extension of this kindred and through replication. © 19

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600607

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

年代:1995

数据来源: WILEY

摘要:

AbstractNumerous studies on the involvement of dopamine receptors in the genetics of alcoholism focused on associations between a polymorphism of the D2 dopamine receptor (DRD2) gene and alcohol dependence. However, the results of these studies are conflicting. Another receptor, the D3 dopamine receptor (DRD3), may be of additional interest since it is specifically located in the limbic area, and in particular in the nucleus accumbens which plays a significant role in the reward process of addiction behavior. We thus tested the association in three independent samples of alcoholic patients, with different origins and various inclusion criteria. No difference in the DRD3 gene polymorphism emerged between controls and alcoholic patients, regardless of their origin, inclusion criteria, or presence or absence of the DRD2 TaqI A1‐allele. Despite the fact that more information could have been considered and that association studies provide limited information, there is good evidence that this DRD3 polymorphism does not play a major role in the genetic component of alcoholism. © 1995 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600608

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

年代:1995

数据来源: WILEY

摘要:

AbstractA recent report of a possible linkage of bipolar affective disorder to a pericentric region of chromosome 18 initiated the present investigation to search for a similar linkage in 32 families with schizophrenia. The results of a study using 5 markers mapped to this region show negative lod scores and only weak evidence for any linkage by nonparametric analyses. If the previously reported finding is a true positive linkage for bipolar disorder, then either it is unlikely to be related to the genetics of schizophrenia, or the proportion of families linked to this region is small. © 1995 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600609

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe studied the neurodevelopmental profile of infants and toddlers with oculo‐auriculo‐vertebral spectrum (OAV) and determined if certain physical manifestations were indicative of a poor neurodevelopmental prognosis. Twenty‐four patients with OAV, aged birth to 57 months, were seen in the Department of Medical Genetics at Children's National Medical Center for multidisciplinary evaluations, including neurodevelopmental assessments.Fifty‐eight percent of these children scored more than 2 standard deviations below the mean in at least one domain of development. There was no difference in developmental outcome of boys versus girls, children affected unilaterally on the right side versus left side, and those with severe clinical manifestations versus those with a milder form. Children with OAV and abnormal muscle tone had lower cognitive, gross motor, and expressive language scores (P= 0.05,P= 0.002, andP= 0.02, respectively). Those affected bilaterally had lower cognitive, fine motor, receptive language, and expressive language scores (P= 0.06,P= 0.03,P= 0.03,P= 0.02, respectively). Children with cervical spine abnormalities had lower cognitive, fine motor, and expressive language scores (P= 0.02,P= 0.04, andP= 0.04, respectively).We conclude that infants and toddlers with OAV are at increased risk for neurodevelopmental delay, especially those with abnormal muscle tone, bilateral involvement, and cervical vertebral anomalies. The complexity of the neurodevelopmental problems is strongly suggestive of central nervous system disturbances. Patients with OAV need comprehensive evaluation by a multi‐disciplinary team to define potential neurodevelopmental delays, allow for early intervention services, and promote an optimal developmental outcome. © 1995 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600610

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe have examined the hypothesis that a variable number of tandem repeats in the third cytoplasmic loop of the dopamine D4 receptor influences clinical response to clozapine using a sample of 189 schizophrenic patients. Alleles of the 48‐bp repeat, which range from two to ten copies in the normal human population, were analysed by the polymerase chain reaction using genomic DNA as template. Association between these alleles and response to clozapine was tested using the difference in pre‐and post‐treatment GAS scores as a measure of response. We found no statistically significant variation between genotypic groups and response by analysis of variance. We conclude that the variation of the number of 48‐bp repeats alone does not determine response to clozapine. Larger studies are underway to determine if there is a more subtle relationship with sequence variation within the repeats or at other polymorphic sites within the gene that may provide evidence for a component of clozapine's action being at D4 receptors. © 1995 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600611

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

年代:1995

数据来源: WILEY