Search PubMed⌕ Search

Biomedical subjects

W T Brown

Publications and source records attributed to W T Brown.

At least 145 records · Page 8Linked to original sources
PubMed1985

Fragile X syndrome: associated neurological abnormalities and developmental disabilities.

The fragile X syndrome is a frequent cause of developmental disabilities. It is associated primarily with nonprogressive X-linked mental retardation. The neurodevelopmental abnormalities of 25 males and 3 females are described. Mental retardation was mild in 4, moderate in 11, severe in 6, and profound in 2 patients, while 4 patients had only learning disabilities. The presence or absence of a developmental disability could not be determined in the youngest (8 months). Seven patients had had infantile autism and 7 had epilepsy. Generally no major focal neurological abnormalities were observed but most of the patients exhibited minor signs. The severity of developmental disabilities in our patients varied between and within families and between genders. All adult males had macroorchidism. Unusual facial features were present in 13 males but none were seen in the females. Familial occurrences were found in 18 cases (64%); 10 cases (36%) were sporadic. Overall, males were more severely affected than females. Diagnostic tests including computed tomographic scans, electroencephalograms, and evoked potentials did not disclose any specific abnormalities.

Adolescent↗
PubMed1985

Analysis of the fragile-X chromosome: localization and detection of the fragile site in high resolution preparations.

Fragile X chromosome preparations were analyzed at levels of up to 850 bands per haploid set. We were able to consistently sublocalize the Xqter fragile site to band Xq27.3 using high-resolution methods. Chromosome length versus the frequency of fragile X expression was also compared. The fragile site appeared at a higher percentage in more condensed chromosome preparations. The importance of this finding is that high-resolution chromosome preparations do not optimize fragile-X detection.

Chromosome Banding↗
PubMed1985

Genetic linkage heterogeneity in the fragile X syndrome.

Genetic linkage between a factor IX DNA restriction fragment length polymorphism (RFLP) and the fragile X chromosome marker was analyzed in eight fragile X pedigrees and compared to eight previously reported pedigrees. A large pedigree with apparently full penetrance in all male members showed a high frequency of recombination. A lod score of -7.39 at theta = 0 and a maximum score of 0.26 at theta = 0.32 were calculated. A second large pedigree with a nonpenetrant male showed tight linkage with a maximum lod score of 3.13 at theta = 0, a result similar to one large pedigree with a nonpenetrant male previously reported. The differences in lod scores seen in these large pedigrees suggested there was genetic heterogeneity in linkage between families which appeared to relate to the presence of nonpenetrant males. The combined lod score for the three pedigrees with nonpenetrant males was 6.84 at theta = 0. For the 13 other pedigrees without nonpenetrant males the combined lod score was -21.81 at theta = 0, with a peak of 0.98 at theta = 0.28. When lod scores from all 16 families were combined, the value was -15.14 at theta = 0 and the overall maximum was 5.13 at theta = 0.17. To determine whether genetic heterogeneity was present, three statistical tests for heterogeneity were employed. First, a "predivided-sample" test was used. The 16 pedigrees were divided into two classes, NP and P, based upon whether or not any nonpenetrant males were detected in the pedigree. This test gave evidence for significant genetic heterogeneity whether the three large pedigrees with seven or more informative males (P less than 0.005), the eight pedigrees with three informative males (P less than 0.001), or all 16 pedigrees (P less than 0.001) were included in the analysis. Second, Morton's large sample test was employed. Significant heterogeneity was present when the analysis was restricted to the three large pedigrees (P less than 0.025), or to the eight pedigrees with informative males (P less than 0.05) but not when smaller, less informative pedigrees were also included. Third, an "admixture" test for heterogeneity was employed which tests for linkage versus no linkage. A trend toward significance was seen (0.05 less than P less than 0.10) which increased when the analysis was restricted to the larger, more informative pedigrees.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Adult fragile X syndrome. Clinico-neuropathologic findings.

Fragile X syndrome [fra (X)] is currently accepted as the second most frequent chromosomal disorder associated with developmental disability. Although next to Down syndrome in frequency, no postmortem studies of confirmed adult cases had been reported. The autopsy examination of a 62-year-old, moderately retarded man with the fra (X) syndrome confirmed the preferential involvement of cerebral and testicular structures in this disorder. Dendritic spine abnormalities of the type observed in trisomic chromosomal disorders were associated with synaptic immaturity. Severe testicular hypogonadism accompanied bilateral macro-orchidism, normal penis, and unilateral hydrocele. Valvular, articular, and testicular interstitial compartments showed normal histochemical staining characteristics for glycoproteins and lipids.

Brain↗
PubMed1985

Mitral valve prolapse and hyperthyroidism: effect of patient selection.

Patients with mitral valve prolapse and hyperthyroidism have common symptoms; the most outstanding symptom is palpitation. To determine whether or not common symptoms contributed to the reported association of these conditions, we evaluated 220 patients with symptomatic mitral valve prolapse and 216 first-degree relatives in 72 families; 65 relatives with mitral valve prolapse and 151 relatives without mitral valve prolapse, all greater than or equal to 16 years of age. Thirty subjects, aged 49 +/- 13 years (p less than 0.025 vs entire study group), had thyroid disease (23 subjects had definite thyroid disease, seven subjects had probable); 27 of 30 subjects with thyroid disease (90%) were female (p less than 0.005). The age- and sex-adjusted prevalence of hyperthyroidism was significantly higher in probands with mitral valve prolapse than in family members without mitral valve prolapse (3.5% vs 0%, p = 0.03), while an intermediate prevalence of hyperthyroidism (2.2%) was observed in family members with mitral valve prolapse. Thus, the prevalence of hyperthyroidism is increased among symptomatic patients with mitral valve prolapse as compared to family members without mitral valve prolapse, but the prevalence of thyroid conditions is similar among family members with or without this condition. These findings are explained by the effect of common symptoms on clinical detection of both mitral valve prolapse and hyperthyroidism.

Adolescent↗
PubMed1985

Cystathionine disappearance with neuronal loss: a possible neuronal marker.

Cystathionine is an important intermediate in the transsulfuration pathway of methionine catabolism and is normally present in high concentration in the human CNS. We have measured the concentration of cystathionine, other amino acids, and brain proteins in the cerebral cortex, cerebellar cortex and spinal cord of two cases with ceroid lipofuscinosis. Neuropathological and biochemical studies of Case 1, at an advanced stage, Case 2, at an early stage, and five controls were correlated with clinical and neurological findings. The concentration of an unidentified 54,000 Dalton protein was greatly increased in Case 1 as observed by 2-D gel electrophoresis. Neurons and cystathionine were almost totally absent from the cortex and cerebellum of Case 1, while they were slightly reduced in Case 2, in comparison to control brains. These studies suggest that cystathionine may be specifically located within neurons. We present for the first time the observation that there was a strikingly low brain concentration of cystathionine, a potential neuronal marker, in an advanced stage of a neurodegenerative process.

Adolescent↗
PubMed1985

Chromosomal localization of several families of repetitive sequences by in situ hybridization.

Four recombinant DNA clones (H1, H7, H12, and H15) carrying low-repetitive human DNA were previously isolated from a human genomic library based on their specificity for chromosome 21 and were studied for their distribution as determined by in situ hybridization. Clone H7 hybridized to the satellite regions of chromosomes 13, 14, 15, 21, and 22 as well as to the centromere region of chromosome 1. Clone H12 hybridized strongly to chromosomes 11 and 17 and the centromere of the X. Clones H1 and H15 had a very widespread distribution throughout the genome. Clone H15 hybridized significantly more to the short arm of chromosome 18 than to any other chromosomal segment. Clone H1 hybridized strongly to the centromere of chromosome 19 and also showed random distribution on all the other human chromosomes. We conclude that these probes appear to represent four repetitive families that demonstrate in situ hybridization patterns that do not correspond with those of any other repetitive family. Further, the in situ hybridization patterns do not show the strong chromosome 21 specificity originally defined by Southern blot analysis. The nature and chromosomal localization of these repetitive families should be useful in regional mapping and evolutionary studies and give additional insight into chromosomal organization.

Chromosome Banding↗
PubMed1984

Isolation and regional localization by in situ hybridization of a unique gene segment to chromosome 21.

V chromosome 21 (ch. 21) flow-sorted library was screened for the presence of unique DNA segments which are specific for the 21st chromosome. By combining the techniques of somatic cell genetics and in situ hybridization, we have identified several of these recombinant probes and have regionally mapped one of them to the distal half of the long arm of chromosome 21 (q22.1- greater than qter). This represents the first report of the sublocalization of a unique DNA segment to chromosome 21 by in situ hybridization.

Animals↗
PubMed1984

Lack of association between dermal arches and mitral valve prolapse: relation to anxiety.

Mitral valve prolapse (MVP) has been reported to be associated with an increased frequency of dermal arches. To determine whether dermal arches are associated with MVP, 42 patients with echocardiographic (echo) MVP (probands) and 140 first-degree relatives in their families, including 48 with and 92 without MVP, were studied. Seventy-five, subjects with neither MVP nor blood relation to probands served as control subjects. Among the female probands, 6.9% had arches and among the males, 3.8% had arches. The proportion of arches was lower among female control subjects (4.0%) but higher among male control subjects (7.9%) (neither difference being significant [NS]). Among the relatives, 7.1% of the women with MPV and 4.6% of the women without MVP had arches (NS). Five percent of the men with MVP and 6.3% without MVP had arches (NS). No association existed between the occurrence of cardiovascular symptoms in patients and family members with MVP and presence of dermal arches, but a high proportion of probands with elevated trait anxiety without panic disorder had 4 or more dermal arches. These findings do not support a direct association of dermal arches with MVP.

Adolescent↗
PubMed1984

Experience with prenatal fragile X detection.

We have attempted the prenatal detection of the fra(X) 9 times. Three fra(X) positive fetuses have been diagnosed: 2 males and one female. The diagnosis on the 2 males has been confirmed. The testes of the 2 fra(X) positive fetuses appeared large for gestational age. However, results of anthropometric, bone age, anatomical and neurohistological studies were normal. Normal outcome was confirmed after birth in 2 males and one female on the basis of whole blood fra(X) studies. A presumptively positive female and a presumptively negative female await confirmation. Two presumptively negative males remain unborn. Further experience is needed to establish the reliability of the prenatal detection of fra(X) (q27).

Adrenal Cortex↗
PubMed1984

Folic acid therapy in the fragile X syndrome.

Two brothers with fra(X) positive X-linked mental retardation (XLMR) were treated with folic acid. Initially a double blind cross-over design was employed followed by a long-term high dose trial. A decrease in the frequency of fra(X) positive cells was observed when low folic acid culture medium was used but not when an FUdR induction system was employed. Selected behavioral characteristics improved in both while receiving folic acid. Decreased hyperactivity, greater attention span, increased motor coordination, increased quantity and quality of speech were noted. Improvement in Leiter mental age and regression after cessation of treatment was seen in one subject but not in the other. Further controlled trials with larger numbers of subjects using high doses of folic acid over longer periods of time are needed to assess the possible benefits of this experimental form of treatment.

Adolescent↗