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Biomedical subjects

T D Bird

Publications and source records attributed to T D Bird.

At least 109 records · Page 6Linked to original sources
PubMed1994

Hereditary neuralgic amyotrophy and hereditary neuropathy with liability to pressure palsies: two distinct genetic disorders.

Hereditary neuralgic amyotrophy with predilection for the brachial plexus (HNA) and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant disorders associated with episodic, recurrent brachial neuropathies. HNPP is associated with a deletion or abnormal structure of the PMP22 gene on chromosome 17p11.2-12. The genetic locus for HNA is unknown. To address the possibility that HNPP and HNA might be identical disorders or allelic variations at the same locus, we investigated three HNA pedigrees with markers from the HNPP region. We did not find the 17p11.2-12 deletion associated with HNPP, nor an abnormality in PMP22 structure with HNA. This analysis provides genetic evidence, in addition to that suggested by the clinical, electrophysiologic, and pathologic differences, that HNA and HNPP are distinct disorders.

Adolescent↗
PubMed1993

Risk factors for suicide in Huntingtons disease: a retrospective case controlled study.

We reviewed 11 instances of suicide in HD families to determine what clinical and social characteristics might alert health professionals to increased suicide potential. The subjects were eight males and one female affected with HD, one female at risk for HD, and one unaffected female spouse, ranging in age from 24 to 65 years. Six of the nine individuals with HD who committed suicide were single or divorced. Duration of HD symptoms ranged from 1 to 14 years. The single most important risk factor for suicide in HD was having no offspring. Other suicides in the family, being unmarried, having contact with others affected with HD, living alone, and depression slightly increased the risk of suicide. The suicide of an unaffected spouse and an individual at risk, but unaffected, emphasizes the heavy burden of HD on other family members. Recognition of these risk factors should allow health care providers to assist families coping with HD and presymptomatic diagnosis.

Adult↗
PubMed1993

DNA deletion associated with hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that causes episodes of focal demyelinating neuropathy following minor trauma to peripheral nerves. We assign the HNPP locus to chromosome 17p11.2 and demonstrate the presence of a large interstitial deletion associated with this disorder in three unrelated pedigrees. De novo deletion is documented in one pedigree. The deleted region appears uniform in all pedigrees and includes the gene for peripheral myelin protein 22 (PMP-22), suggesting that underexpression of PMP-22 may cause HNPP. The deletion in HNPP spans approximately 1.5 Mb and includes all markers that are known to map within the Charcot-Marie-Tooth neuropathy type 1A (CMT1A) duplication. Furthermore, the breakpoints in HNPP and CMT1A map to the same intervals in 17p11.2, suggesting that these genetic disorders may be the result of reciprocal products of unequal crossover.

Chromosome Mapping↗
PubMed1993

Conjugal Alzheimer's disease: is there an increased risk in offspring?

Thirty-one couples in which both spouses had the clinical diagnosis of Alzheimer's disease (AD) (confirmed by autopsy in 12) were ascertained. The mean age of onset of dementia was 75.1 +/- 7.4 years. These couples had 87 children, 63 still living. Seventeen (19.5%) of the children developed dementia, with a mean age of onset of 68.9 +/- 8.3 years. Thirty of the children of the conjugal AD couples survived to age 65 or longer and 14 (47%) of them developed dementia. This prevalence of dementia in the children of affected couples is much greater than that in the children of two control groups consisting of 234 couples in which one spouse had AD and 192 couples in which neither spouse was demented. Twenty-one of the conjugal AD couples had a family history of AD but the prevalence of dementia in their children was not greater than that in the children of conjugal AD couples without a family history of AD. These results represent additional evidence of an important genetic component in late-onset AD and provide empirical risk data for the children of conjugal AD couples.

Adult↗
PubMed1993

The Seattle Alzheimer's disease data set.

Forty families submitted to Genetic Analysis Workshop 8 are described. These are the families in the Seattle data set which have been typed for at least one genetic marker from the centromeric region of chromosome 21 or the q arm of chromosome 19. Thirteen of these families have average ages of onset below age 61 and are therefore considered to be early onset families. Seven of the families are of Volga German descent. Thirty-four of the families have autopsy documented Alzheimer's disease, including all 13 of the early onset pedigrees. The data set includes both the clinical and pedigree information available on the portions of the pedigrees used in the linkage analyses, genotype data on three loci on chromosome 19 and four loci on chromosome 21, and more extended family data on individuals who have not been included in the linkage analyses.

Adult↗
PubMed1993

Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene.

P0, a major structural protein of peripheral myelin, is a homophilic adhesion molecule and maps to chromosome 1q22-q23, in the region of the locus for Charcot-Marie-Tooth neuropathy type 1B (CMT1B). We have investigated P0 as a candidate gene in two pedigrees with CMT1B and found point mutations which are completely linked with the disease (Z = 5.5, theta = 0). The mutations, glutamate substitution for lysine 96 or aspartate 90, are located in the extracellular domain, which plays a significant role in myelin membrane adhesion. Individuals with CMT1B are heterozygous for the normal allele and the mutant allele. Our results indicate that P0 is a gene responsible for CMT1B.

Alleles↗
PubMed1993

Lack of detectable radiation hypersensitivity in lymphoblastoid cells from multiple pedigrees of familial Alzheimer disease.

Recent reports suggest that cultivated nonneuronal cells from individuals with Alzheimer disease (AD) and other specific hereditary neurodegenerative disorders show hypersensitivity to DNA-damaging agents such as x-rays and radiomimetic chemicals. The hypothesis proposed is that a number of chronic neurologic degenerations, including AD, may be the result of accumulation of damaged DNA, resulting from a defect in DNA repair. We investigated this hypothesis by evaluating cells from individuals from pedigrees of familial Alzheimer disease (FAD) for hypersensitivity to x-irradiation. Sensitivity was assayed by viability measured by trypan blue dye exclusion and micronucleus formation. We tested B-lymphoblastoid cell lines from nine patients and nine unaffected family members from pedigrees with FAD, three unrelated controls, three ataxia telangiectasia (AT) patients, and three Down syndrome individuals. The AT cell lines showed the expected reduced viability and increased micronucleus formation after x-ray treatment. The FAD and control lines showed marked heterogeneity with both assays. There was no significant differences between the FAD patients and controls. The wide variability in the response of cell lines from controls and patients indicates the need for more sensitive assays for detection of radiation sensitivity in cells from various neurologic disorders.

Aged↗
PubMed1993

Comparison of the severity of neuropathologic changes in familial and sporadic Alzheimer's disease.

We compared the density of neurofibrillary tangles (NT) and neuritic (senile) plaques (NP) in 10 cortical areas, the amygdala, the hippocampus, the parahippocampal gyrus, and the cerebellum in patients with familial (FAD) and sporadic (SAD) Alzheimer's disease with early (< 55 years), intermediate (55-70 years) and late (> 70 years) ages of onset of dementia and age-matched controls. From a total of 199 cases of pathologically confirmed AD in our laboratory, 60 cases with appropriate brain sections and information as to family history, age of onset, duration of dementia, and brain weight were available for semiquantitative analysis of the frequency of NT and NP utilizing the Consortium to Establish a Registry for Alzheimer's Disease protocol. There were 28 SAD and 32 FAD (including seven Volga Germans) cases and 16 age-matched controls. In all brain regions, cases had more severe changes than controls (p < 0.001). Brain weight correlated inversely with duration of disease (p < 0.001). No significant differences were found in the severity scores of NT and NP between FAD and SAD. There was an inverse correlation between age of onset of dementia and the density of NT and NP in all regions in FAD and SAD combined. P values for NT were in the frontal (superior-middle and orbital, p < 0.0005; gyrus rectus, p = 0.0029), parietal (p = 0.0007), and medial occipital cortex (areas 17 and 18, p < 0.01), and for NP were in the superior temporal gyrus (p = 0.0085) and area 17 (p = 0.0003), and age of onset of dementia. In summary, using these criteria we found no compelling evidence that the neuropathologic characteristics of FAD are different from those of SAD.

Aged↗
PubMed1992

Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14.

Linkage analysis was used to search the genome for chromosomal regions harboring familial Alzheimer's disease genes. Markers on chromosome 14 gave highly significant positive lod scores in early-onset non-Volga German kindreds; a Zmax of 9.15 (theta = 0.01) was obtained with the marker D14S43 at 14q24.3. One early-onset family yielded a lod score of 4.89 (theta = 0.0). When no assumptions were made about age-dependent penetrance, significant results were still obtained (Zmax = 5.94, theta = 0.0), despite the loss of power to detect linkage under these conditions. Results for the Volga German families were either negative or nonsignificant for markers in this region. Thus, evidence indicates a familial Alzheimer's disease locus on chromosome 14.

Alzheimer Disease↗
PubMed1992

Genetic association and linkage analysis of the apolipoprotein CII locus and familial Alzheimer's disease.

We previously reported a genetic association between the 3.5 kb (F) Taq I restriction fragment length polymorphism allele of the apolipoprotein CII gene on chromosome 19 and familial Alzheimer's disease. Here, we report an additional analysis of this association performed on an expanded and better defined data set of 23 families with familial Alzheimer's disease. The F allele frequency in affected family members in the expanded set was 0.62 +/- 0.06 (mean +/- standard error, n = 51 subjects), which differed significantly from a frequency of 0.39 +/- 0.02 (n = 226) for unrelated control subjects (Z = 3.75, p less than 0.0002). These results are consistent with our previous findings and suggest an association between the F allele of apolipoprotein CII and familial Alzheimer's disease. When the apolipoprotein CII locus was tested for linkage to familial Alzheimer's disease, LOD scores summed for the complete group of families were negative and close linkage was excluded. Close linkage was also excluded for early-onset families (mean onset age less than or equal to 60 years), but small positive LOD scores were obtained for late-onset kindreds.

Alleles↗
PubMed1992

Peripheral myelin protein-22 gene maps in the duplication in chromosome 17p11.2 associated with Charcot-Marie-Tooth 1A.

Charcot-Marie-Tooth disease 1A (CMT1A) is a hereditary demyelinating peripheral neuropathy, associated with a DNA duplication on chromosome 17p11.2. A related disorder in the mouse, trembler (Tr), maps to mouse chromosome 11 which has syntenic homology to human chromosome 17p. Recently, the peripheral myelin protein-22 (pmp-22) gene was identified as the likely Tr locus. We have constructed a partial yeast artificial chromosome contig spanning the CMT1A gene region and mapped the PMP-22 gene to the duplicated region. These observations further implicate PMP-22 as a candidate gene for CMT1A, and suggest that over-expression of this gene may be one mechanism that produces the CMT1A phenotype.

Animals↗
PubMed1992

Familial presenile dementia with psychosis associated with cortical neurofibrillary tangles and degeneration of the amygdala.

We report a family in which 13 members in three generations had the presenile (age 42 to 66 years) onset of dementia with an autosomal dominant pattern of inheritance. An early symptom in eight individuals was prominent antisocial psychotic or belligerent behavior, often leading to the initial clinical diagnosis of paranoid schizophrenia. Duration of illness was longer than is usual in Alzheimer's disease (AD), ranging from 14 to 26 years in six members. Three affected siblings and a cousin have come to autopsy, and all had neurofibrillary tangles without senile plaques in several regions of the neocortex, amygdala, and parahippocampal gyrus. The hippocampus was free of both neurofibrillary tangles and senile plaques in all four, but in three there was neuronal loss with gliosis in the CA1 region of Ammon's horn bilaterally. There also was neuronal loss and neurofibrillary tangles in the nucleus basalis. The neurofibrillary tangles were tau-2 and Alz-50 positive and were composed of paired helical filaments ultrastructurally. The disease in this kindred appears to be a unique hereditary disorder that is distinct from familial AD.

Alzheimer Disease↗