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W T Brown

Publications and source records attributed to W T Brown.

At least 109 records · Page 6Linked to original sources
PubMed1991

Why are autism and the fragile-X syndrome associated? Conceptual and methodological issues.

Investigations of the association between autism and the fragile-X syndrome have yielded conflicting results with some studies indicating a strong correlation and others indicating no relation between the disorders. In this paper, we review the relevant research on this controversy and discuss the conceptual and methodological problems involved in such an inquiry. We conclude that autism and fragile X are associated and that this relation will prove fruitful in understanding the role of the X chromosome in a variety of behavior disorders and in unraveling various theoretical accounts on the etiology of autism.

Autistic Disorder↗
PubMed1990

Creutzfeldt-Jakob disease and kuru patients lack a mutation consistently found in the Gerstmann-Sträussler-Scheinker syndrome.

We and others have recently reported that patients with the Gerstmann-Sträussler-Scheinker syndrome have a mutation at codon 102 of the gene coding for amyloid protein that accumulates in this disease. We report here that this mutation was not found in 5 familial and 27 sporadic cases of Creutzfeldt-Jakob disease or in 3 patients with kuru, so that although this mutation may be responsible for amyloidogenesis and transmissibility in Gerstmann-Sträussler-Scheinker syndrome, it cannot be the only cause of human spongiform encephalopathy.

Base Sequence↗
PubMed1990

Monozygotic twins with trisomy 18: a report of discordant phenotype.

The predicted incidence of liveborn monozygotic trisomy 18 twins is one per million births. The first case of liveborn monozygotic trisomy 18 twins was reported in 1989 and we report a second case in which striking phenotypic discordance existed. The probability of monozygotic trisomy 18 twinning and the mechanisms for phenotypic discordance in trisomic twins is discussed.

Abnormalities, Multiple↗
PubMed1989

Mutations in familial Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker's syndrome.

A host protein encoded by the gene specifying the scrapie amyloid precursor affects pathogenesis of the transmissible spongiform encephalopathies: Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker's syndrome (GSS), and kuru in man, and scrapie in animals. We found a mutation in this gene of two patients with CJD from one family and a second mutation in the same gene in three patients with GSS from another family. The mutation in two related familial CJD patients changed glutamine in position 200 tolysine. This mutation was absent in other individuals including unrelated patients with familial CJD, sporadic CJD, and GSS. The other mutation in three GSS patients changed proline in position 102 to leucine, the same mutation described recently in some GSS families. We did not find it in six unaffected relatives of the GSS patients or in other individuals including sporadic and familial CJD patients. A rare insertion described earlier in one CJD family was also absent in all tested individuals.

Base Sequence↗
PubMed1989

Parent-child dyadic gaze patterns in fragile X males and in non-fragile X males with autistic disorder.

Parent-child dyadic gaze patterns were examined in fragile X [fra(X)] males and in non-fra(X) autistic males across three age groups--early childhood, middle childhood and adolescence. Absolute probabilities of social gaze did not significantly differ across diagnostic groups. Event lag sequential analyses indicated that fra(X) males were sensitive to social gaze initiation by their parents but found eye contact aversive. Non-fra(X) autistic males, by contrast, were insensitive to parent-initiated social gaze, and did not find eye contact aversive. Implications for research on the social characteristics of fra(X) and autistic children are discussed.

Adolescent↗
PubMed1989

The fragile X syndrome.

Males who possess the fragile X chromosome, a marker on the end of the X chromosome at position Xq27.3, have a distinct form of mental retardation, which has come to be known as the fragile X [fra(X)] syndrome. This X-linked syndrome is the most common Mendelian form of mental retardation. Males who inherit the fra(X) chromosome are usually moderately to severely retarded. There are also normal carrier men who are nonpenetrant for the mutation. They transmit the mutation to their daughters, who can have affected sons. The development of methods for detecting fra(X) in blood and amniotic fluid cells has allowed for population screening and prenatal diagnosis of the syndrome. New methods using DNA probes and restriction fragment length polymorphisms (RFLPs) are being applied to study the inheritance of fra(X). They have revealed apparent genetic linkage heterogeneity. Molecular studies to analyze the underlying mutation are underway to define the structural basis.

Fragile X Syndrome↗
PubMed1989

Beta-amyloid protein probe hybridized to chromosome 9 in 3 Alzheimer disease individuals.

We have reported recently the sublocalization of an Alzheimer Disease-associated gene that encodes for cerebrovascular beta-amyloid protein (BAP). Its locus appears to be at or proximal to band 21q2105 through band 21q11.1. We have also observed hybridization to chromosome 20 in normal and Down syndrome individuals using the single-stranded form of the probe. Further, we have found that BAP hybridizes to chromosome 9 in lymphoblastoid cells from three individuals from two families with familial Alzheimer Disease (AD). We have now obtained additional data which shows significant hybridization to chromosomes 9,20 and 21 for two normal control individuals, a Down syndrome (DS) individual and three AD individuals. When the normal and Down Syndrome individuals were compared to the group of individuals with AD, significant hybridization to chromosome 9 occurred in the Alzheimer group only (p less than .05). Almost half of the silver grains on chromosome 9 in the three AD individuals were localized to the distal area of the long arm. Whether these observations demonstrate an apparent genetic marker in these three individuals with familial AD, or whether our observations have identified a marker for both familial and sporadic AD will be determined by further studies.

Alzheimer Disease↗
PubMed1988

Fine mapping of an Alzheimer disease-associated gene encoding beta-amyloid protein.

We have sublocalized an Alzheimer Disease-associated gene, which encodes for cerebrovascular beta-amyloid protein, to the region from the centromere through the proximal half of band 21q21 using both somatic cell and in situ mapping techniques. In addition we found repeatedly significant but weaker hybridization of the beta-amyloid protein probe to the short arm of chromosome 20. 794 cells were analyzed from whole blood, lymphoblastoid and skin cultures. The latter two types of cultures had parts of the 21st chromosome translocated to other chromosomes facilitating sublocalization.

Alzheimer Disease↗
PubMed1988

Multilocus analysis of the fragile X syndrome.

A multilocus analysis of the fragile X (fra(X] syndrome was conducted with 147 families. Two proximal loci, DXS51 and F9, and two distal loci, DXS52 and DXS15, were studied. Overall, the best multipoint distances were found to be DXS51-F9, 6.9%, F9-fra(X), 22.4%; fra(X)-DXS52, 12.7%; DXS52-DXS15, 2.2%. These distances can be used for multipoint mapping of new probes, carrier testing and counseling of fra(X) families. Consistent with several previous studies, the families as a whole showed genetic heterogeneity for linkage between F9 and fra(X).

Chromosome Mapping↗
PubMed1988

Social gaze, social avoidance, and repetitive behavior in fragile X males: a controlled study.

Preference for social gaze as well as the percentage occurrence of social gaze, nonverbal social avoidance, and nonverbal repetitive behaviors were examined in autistic and nonautistic prepubertal males with the fragile X syndrome (fra[X]) during social interaction with a parent or stranger. Comparison groups were nonhandicapped, Down syndrome, atypical pervasive developmental disorder, and autistic males. The subjects with fra(X) and the nonhandicapped and Down syndrome control subjects discriminated parent from stranger as evidenced by their avoidance behavior. The overall percentage of avoidance was higher, however, for both parent and stranger, among the males with fra(X). Autistic and atypical groups without fra(X) failed to discriminate parent from stranger in their avoidance behavior. Possible explanations for these group differences in terms of language level or degree of language demand were ruled out. Implications for research concerning the relations among fra(X), autism, and mental retardation were discussed.

Autistic Disorder↗