Search PubMed⌕ Search

Biomedical subjects

T D Bird

Publications and source records attributed to T D Bird.

At least 127 records · Page 7Linked to original sources
PubMed1992

Analysis of the DNA duplication 17p11.2 in Charcot-Marie-Tooth neuropathy type 1 pedigrees: additional evidence for a third autosomal CMT1 locus.

We have restudied two clinically typical Charcot-Marie-Tooth neuropathy type 1 (CMT1; also known as hereditary motor and sensory neuropathy 1) pedigrees that were previously reported to be unlinked to the regions of proximal chromosome 1q and chromosome 17p by multipoint linkage analyses. In these two pedigrees, there is no evidence for linkage to additional DNA markers that flank and span the CMT1A locus on chromosome 17p11.2, and a duplication associated with CMT1A is not present in these pedigrees. These findings confirm that the CMT1 locus in these two pedigrees does not map to chromosome 17p11.2 or 1q, and provide further evidence for the existence of a third autosomal locus for CMT1.

Charcot-Marie-Tooth Disease↗
PubMed1992

Trisomy 17p associated with Charcot-Marie-Tooth neuropathy type 1A phenotype: evidence for gene dosage as a mechanism in CMT1A.

Charcot-Marie-Tooth neuropathy type 1A (CMT1A) is associated with a DNA duplication on chromosome 17, band p11.2, resulting in partial trisomy for this region in CMT1A patients. The 17p11.2 duplication may lead to the CMT1A phenotype either through disruption of a gene at the duplication breakpoint junction or by trisomic dosage and overexpression of a gene within the duplication. To test the latter model, we evaluated a patient with complete translocation trisomy 17p for signs of CMT1A. In addition to the dysmorphic features seen in trisomy 17p, a neurologic examination and electrophysiologic studies detected a demyelinating neuropathy, compatible with CMT1A. A karyotype on the patient's father found a balanced translocation [t(14;17)] with breakpoints on chromosome 17 in either band p11.1 or proximal p11.2. An analysis of the patient's DNA confirmed trisomy 17p and mapped the translocation breakpoint to a region in 17p11.2, proximal to the duplication breakpoint in CMT1A. Our observations in this patient with trisomy 17p are relevant to an understanding of the genetic mechanism in CMT1A and provide strong evidence that gene dosage through segmental trisomy for 17p11.2 results in the CMT1A phenotype.

Adolescent↗
PubMed1992

Multicolor in situ hybridization and linkage analysis order Charcot-Marie-Tooth type I (CMTIA) gene-region markers.

This study demonstrates a clear and current role for multicolor in situ hybridization in expediting positional cloning studies of unknown disease genes. Nine polymorphic DNA cosmids have been mapped to eight ordered locations spanning the Charcot-Marie-Tooth type 1 (CMT1A) disease gene region in distal band 17p11.2, by multicolor in situ hybridization. When used with linkage analysis, these methods have generated a fine physical map and have firmly assigned the CMT1A gene to distal band 17p11.2. Linkage analysis with four CMT1A pedigrees mapped the CMT1A gene with respect to two flanking markers (8B10-5 cM[LOD 5.2]-CMT1A-3.5 cM[LOD 5.3]-10E4). Additional loci were physically mapped and ordered by in situ hybridization and analysis of phase-known recombinants in CMT1A pedigrees. The order determined by multicolor in situ hybridization was 17cen-LEW301-8B10-5H5/6A9-VAW409- 5G7-6G1-4A11-VAW412-10E4-pter. Two ordered probes, 4A11 and 6G1, reside on the same 440-kb partial SfiI restriction fragment. These data demonstrate the ability of in situ hybridization to resolve loci within 0.5 Mb on early-metaphase chromosomes. Multicolor in situ hybridization also excluded the possibility of pericentric inversions in two unrelated patients with CMT1 and neurofibromatosis type 1. When used with pulsed-field gel electrophoresis, multicolor in situ hybridization can establish physical location, order, and distance in closely spaced chromosome loci.

Charcot-Marie-Tooth Disease↗
PubMed1991

Chromosome 1 Charcot-Marie-Tooth disease (CMT1B) locus in the Fc gamma receptor gene region.

The Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy) loci have been reported to be on at least three chromosomes: 1 (CMT1B, HMSN1B), 17 (CMT1A), and X (CMTX). In this study multipoint linkage analysis of two Duffy-linked families given a combined LOD score of 8.65 to establish that the Duffy-linked CMT1B gene exists in the 18 centimorgan region between the antithrombin III gene and the Duffy/sodium-potassium ATPase loci. The simultaneous segregation of polymorphisms near the CMT1A locus on chromosome 17 excludes linkage to this chromosome region in both families. Polymorphic sites that flank the CMT1B gene have been subchromosomally localized to the proximal chromosome-1 long arm (1q21.2----1q25) by spot blot analysis of sorted chromosomes, polymorphic deletion analysis, in situ hybridization, and multipoint linkage analysis.

Antigens, Differentiation↗
PubMed1991

Theophylline-associated seizures with "therapeutic" or low toxic serum concentrations: risk factors for serious outcome in adults.

We report 12 adults with seizures associated with serum theophylline levels between 14 and 35 mg/l. The seizures were frequently prolonged, and outcome was generally poor with eight deaths. Although we did not identify comparable control groups, possible risk factors for serious outcome in theophylline-associated seizures were age, previous brain injury or disease, severe pulmonary disease, and possibly low serum albumin level. In patients with these risk factors, serum theophylline levels should be maintained below 10 to 15 mg/l.

Aged↗
PubMed1991

X-linked sideroblastic anemia and ataxia: linkage to phosphoglycerate kinase at Xq13.

Molecular linkage analysis was performed on a kindred with X-linked sideroblastic anemia and ataxia. Two-point analysis with a DNA probe for phosphoglycerate kinase (PGK1), which maps to Xq13, suggested linkage to the disorder by a lod score of at least 2.60 at a recombination fraction of zero. The disease in this kindred appears to be clinically and genetically distinct from that in previously reported families with X-linked hereditary ataxia or spastic paraparesis. No mapping data are available for inherited X-linked sideroblastic anemia without neurologic abnormalities. However, structural alterations of band Xq13 may be involved in the development of idiopathic acquired sideroblastic anemia. No alterations in the restriction patterns of two X-linked genes involved in erythrocyte formation-i.e., a DNA-binding protein (GF-1) and 5-aminolevulinate synthase (ALAS)-were detected in DNA from affected males, arguing against a large deletion in either of these candidate genes.

Anemia, Sideroblastic↗
PubMed1991

Complete deletion of the proteolipid protein gene (PLP) in a family with X-linked Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is an X-linked neurologic disorder characterized by dysmyelination in the central nervous system. Proteolipid protein (PLP), a major structural protein of myelin, is coded on the X chromosome. It has been postulated that a defect in the PLP gene is responsible for PMD. Different single-nucleotide substitutions have been found in conserved regions of the PLP gene of four unrelated PMD patients. Novel Southern blot patterns suggested a complex rearrangement in a fifth family. Linkage to PLP has been shown in others. We evaluated the PLP locus in a four-generation family with two living males affected with X-linked PMD. Analysis of DNA from the affected males revealed complete absence of a band, with PLP probes encompassing the promoter region, the entire coding region, and the 3' untranslated region and spanning at least 29 kb of genomic DNA. DNA from unaffected relatives gave the expected band pattern. Two obligate and one probable carrier women were hemizygous for the PLP locus by dosage analysis. Although it is unlikely, the previously described point mutations in PLP could represent polymorphisms. The finding of complete deletion of the PLP gene in our family is a stronger argument that mutations in PLP are responsible for X-linked PMD.

Adult↗
PubMed1990

Family with dominantly inherited ataxia, amyotrophy, and peripheral sensory loss. Spinopontine atrophy or Machado-Joseph Azorean disease in another non-Portuguese family?

A family of German extraction with progressive ataxia, eye movement abnormalities, peripheral sensory loss, and spinal muscular atrophy of adult onset is described. Three members came to autopsy, and neuropathologically, the major changes included varying degrees of atrophy of the basis pontis and degeneration of the spinocerebellar tracts, Clarke's columns, anterior horn neurons, and fasciculus gracilis. The dentate nucleus was spared, and there was slight neuron loss from the substantia nigra in one patient. Clinically and neuropathologically, our family resembles that reported by Boller and Segarra as having spinopontine atrophy. However, several kindreds with similar findings have recently been described as having Azorean or Machado-Joseph disease in non-Portuguese families. Comparison of clinical and neuropathological features in spinopontine atrophy and Machado-Joseph disease, both in Portuguese and non-Portuguese families, reveals clinical and pathological similarities and differences between the two. The major differences in our patients include only minor extraocular movement abnormality and absence of protuberant eyes, and muscular rigidity clinically, and the sparing of the substantia nigra and the dentate nucleus neuropathologically. These differences suggest that spinopontine atrophy, as manifested in our family, is distinct from Machado-Joseph disease. Our family showed no linkage to the HLA locus on chromosome 6.

Adult↗
PubMed1990

Cone dysfunction in a subgroup of patients with autosomal dominant cerebellar ataxia.

Four patients with autosomal dominant cerebellar ataxia and retinal degeneration underwent neurologic and ophthalmologic examinations and computer-assessed corneal electroretinography. Previous reports described progressive panretinal degeneration initially involving the cones and subsequently spreading to the rods. By contrast, all our patients displayed evidence of selective dysfunction of the cone system in one or two successive electroretinograms, irrespective of their age or duration of visual symptoms. Color vision testing, funduscopy, and fluorescein angiography suggested a cone dystrophy. Within the period of observation only one patient showed progression of cone dysfunction. In patients with hereditary ataxias, quantitative electroretinography provides an objective and sometimes early indication of retinal degeneration and helps to characterize it.

Adult↗
PubMed1990

Myoclonus, seizures, and paratonia in Alzheimer disease.

Twenty-eight patients with the clinical diagnosis of probable Alzheimer disease (AD) were followed longitudinally until death. The presence of myoclonus, seizures, and paratonia was monitored as part of this process. At autopsy, 22 of the patients met pathologic criteria for AD and 6 had other degenerative neurologic diseases. Myoclonus was present in 55% of the AD patients and none of the non-AD patients. Seizures were present in 64% of the AD patients, and only 17% of the non-AD patients. Paratonia was found frequently in all patient groups. In most patients, symptoms developed late in the course of their illness. The incidence of myoclonus, seizures, and paratonia in our patients was higher than in most previous studies. The reasons for this finding are discussed.

Adult↗
PubMed1990

Neuropathological findings in patients with clinical diagnoses of probable Alzheimer's disease.

To assess prospectively the accuracy of standard antemortem clinical diagnostic criteria for Alzheimer's disease, post-mortem examinations were performed on 25 patients who had met DSM-III criteria for primary degenerative dementia and National Institute of Neurological and Communicative Disorders and Stroke criteria for probable Alzheimer's disease. Seventeen patients (68%) met neuropathological criteria for Alzheimer's disease. Two presenile-onset patients had diffuse neocortical senile plaques of insufficient number for definite Alzheimer's disease. Six patients had non-Alzheimer's disease diagnoses. Five of these six had presenile-onset dementia. These results suggest caution in the antemortem diagnosis of Alzheimer's disease in presenile-onset dementia.

Aged↗
PubMed1990

Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity.

We evaluated age at onset and lifetime risk for Alzheimer's disease (AD) in 70 kindreds with familial AD (designated FAD) composed of 541 affected and 1,066 unaffected offspring of demented parents who were identified retrospectively. Using a survival analysis method which takes into account affected persons with unknown onset ages and unaffected persons with unknown censoring ages, we found lifetime risk of AD among at-risk offspring by age 87 to be 64%. Analysis of age at onset among kindreds showed evidence for a bimodal distribution: in this sample, families with a mean onset age of less than 58 years were designated as having early-onset, while late-onset families had a mean onset age greater than 58 years. At-risk offspring in early-onset families had an estimated lifetime risk for dementia of 53%, which is significantly less than the risk of 86% that was estimated for offspring in late-onset families. Men and women in early-onset families had equivalent risk of dementia. In late-onset families, the risk to female offspring was somewhat higher than to male offspring but this difference was marginally significant. Lifetime risk of dementia in early-onset FAD kindreds is consistent with an autosomal dominant inheritance model. Our results may suggest that late-onset FAD has at least 2 etiologies; AD in some families may be transmitted as a dominant trait, whereas a proportion of cases in these and other late-onset families may be caused by other genetic or shared environmental factors.

Age Factors↗
PubMed1990

Sexual function in married men with Parkinson's disease compared to married men with arthritis.

We evaluated the sexual function of 41 married men with Parkinson's disease (PD) and its relation to age, severity of PD, and depression. We used a group of 29 married men with arthritis for comparison. Total sexual functioning and categories of desire, arousal, orgasm, and satisfaction did not differ significantly between patients with PD and arthritis. For both PD and arthritis, increased age, severity of illness, and depression were associated with reduced sexual function. These results suggest that sexual dysfunction is common in married men with PD, but no more so than in men with another chronic illness that does not involve the nervous system.

Adult↗
PubMed1990

Genetic linkage and heterogeneity in type I Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy type I).

The segregation patterns of DNA markers from the pericentromeric regions of chromosomes 1 and 17 were studied in seven pedigrees segregating an autosomal dominant gene for Charcot-Marie-Tooth neuropathy type I (CMT I; hereditary motor and sensory neuropathy I). A multilocus analysis with four markers (pMCR-3, pMUC10, FY, and pMLAJ1) spanning the pericentromeric region of chromosome 1 excluded the CMT I gene from this region in six pedigrees but gave some evidence for linkage to the region of Duffy in one pedigree. Linkage of the CMT I gene to markers in the pericentromeric region of chromosome 17 (markers pA10-41, pEW301, p3.6, and pTH17.19) was established; however, in these seven pedigrees homogeneity analysis with chromosome 17 markers detected significant genetic heterogeneity. This analysis suggested that three of the seven pedigrees are not linked to this same region. Overall, two of the seven CMT I pedigrees were not linked to markers tested from chromosomes 1 or 17. These results confirm genetic heterogeneity in CMT I and implicate the existence of a third autosomal locus, in addition to a locus on chromosome 17, and a probable locus on chromosome 1. This evidence of etiological heterogeneity, supported by statistical tests, will have to be taken into consideration when fine-structure genetic maps of the regions around CMT I are constructed.

Charcot-Marie-Tooth Disease↗
PubMed1989

Phenotypic heterogeneity in familial Alzheimer's disease: a study of 24 kindreds.

We report the clinical and neuropathological characteristics occurring in 180 demented individuals from 24 kindreds with familial Alzheimer's disease (FAD). Each family had at least two affected generations, and at least one autopsy or brain biopsy was compatible with the diagnosis of AD. Forty-nine neuropathological specimens or reports were reviewed. Mean age of onset for the total group was 54.7 years +/- 11.5, with a large range of 30 to 84 years. Mean age at death was 63.5 years +/- 12.2, with a range of 46 to 85. Mean duration of disease was 8.8 years +/- 4.4, with a range of 1 to 23 years. Six findings suggested phenotypic heterogeneity in FAD. (1) Five families represented an early age of onset group with mean onset at 42 years (range 30 to 51 years) and mean disease duration of 6.7 years. (2) Eight families represented a late onset group with mean onset at 68 years (range 59 to 78 years) and a mean duration of 8.5 years. (3) Seven families were of Volga German ancestry, all originating from the same two villages in Russia. Mean age of onset was 55.9 years (range 40 to 72 years), with a mean disease duration of 10 years. This group probably represents the genetic founder effect of an autosomal dominant gene for AD. (4) One family had the unusual characteristics of neurofibrillary tangles and granulovacuolar change but no amyloid plaques, a mean disease duration of more than 11 years, and a "schizophrenia-like" onset. (5) One family with late onset also had clinical and pathological evidence for anterior horn cell disease. (6) Two autopsies in 1 family both showed remarkable rarefaction of myelin and expansion of perivascular spaces in centrum semiovale (état criblé), with marked leptomeningeal and cortical amyloid angiopathy, distinct from the other FAD brains. It remains to be determined whether the clinical and pathological differences between these families represent genetic heterogeneity at the biochemical or molecular level.

Adult↗
PubMed1989

The genetics of Alzheimer's disease.

Genetic factors play a major role in some if not all cases of Alzheimer's disease (AD). In certain rare families, the disease is most likely inherited as an autosomal dominant trait. Identification of the genes involved in AD is in progress. One AD-related gene, which codes for the amyloid precursor protein (APP), has been cloned and characterized. This gene, though certainly involved in the pathogenesis of AD, is not defective in AD subjects. Genetic linkage analysis of familial Alzheimer's disease (FAD) should help to identify defective genes directly involved in initiating the pathogenesis of AD. In addition, the study of the genes responsible for the Down syndrome (DS) phenotype may yield information on the sequence of events leading to the dementia of AD.

Adolescent↗