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- Almqvist, E, et al.
(författare)
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Ancestral differences in the distribution of the delta 2642 glutamic acid polymorphism is associated with varying CAG repeat lengths on normal chromosomes : insights into the genetic evolution of Huntington disease.
- 1995
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 4:2, s. 207-14
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Tidskriftsartikel (refereegranskat)abstract
- This study addresses genetic factors associated with normal variation of the CAG repeat in the Huntington disease (HD) gene. To achieve this, we have studied patterns of variation of three trinucleotide repeats in the HD gene including the CAG and adjacent CCG repeats as well as a GAG polymorphism at residue 2642 (delta 2642). We have previously demonstrated that variation in the CCG repeat is associated with variation of the CAG repeat length on normal chromosomes. Here we show that differences in the GAG trinucleotide polymorphism at residue 2642 is also significantly correlated with CAG size on normal chromosomes. The B allele which is associated with higher CAG repeat lengths on normal chromosomes is markedly enriched on affected chromosomes. Furthermore, this glutamic acid polymorphism shows significant variation in different ancestries and is absent in chromosomes of Japanese, Black and Chinese descent. Haplotype analysis of both the CCG and delta 2642 polymorphisms have indicated that both are independently associated with differences in CAG length on normal chromosomes. These findings lead to a model for the genetic evolution of new mutations for HD preferentially occurring on normal chromosomes with higher CAG repeat lengths and a CCG repeat length of seven and/or a deletion of the glutamic acid residue at delta 2642. This study also provides additional evidence for genetic contributions to demographic differences in prevalence rates for HD.
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| 2. |
- Almqvist, E, et al.
(författare)
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Risk reversals in predictive testing for Huntington disease.
- 1997
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 61:4, s. 945-52
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Tidskriftsartikel (refereegranskat)abstract
- The first predictive testing for Huntington disease (HD) was based on analysis of linked polymorphic DNA markers to estimate the likelihood of inheriting the mutation for HD. Limits to accuracy included recombination between the DNA markers and the mutation, pedigree structure, and whether DNA samples were available from family members. With direct tests for the HD mutation, we have assessed the accuracy of results obtained by linkage approaches when requested to do so by the test individuals. For six such individuals, there was significant disparity between the tests. Three went from a decreased risk to an increased risk, while in another three the risk was decreased. Knowledge of the potential reasons for these changes in results and impact of these risk reversals on both patients and the counseling team can assist in the development of strategies for the prevention and, where necessary, management of a risk reversal in any predictive testing program.
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| 3. |
- Almqvist, E W, et al.
(författare)
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A worldwide assessment of the frequency of suicide, suicide attempts, or psychiatric hospitalization after predictive testing for Huntington disease.
- 1999
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 64:5, s. 1293-304
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Tidskriftsartikel (refereegranskat)abstract
- Prior to the implementation of predictive-testing programs for Huntington disease (HD), significant concern was raised concerning the likelihood of catastrophic events (CEs), particularly in those persons receiving an increased-risk result. We have investigated the frequency of CEs-that is, suicide, suicide attempt, and psychiatric hospitalization-after an HD predictive-testing result, through questionnaires sent to predictive-testing centers worldwide. A total of 44 persons (0.97%) in a cohort of 4,527 test participants had a CE: 5 successful suicides, 21 suicide attempts, and 18 hospitalizations for psychiatric reasons. All persons committing suicide had signs of HD, whereas 11 (52.4%) of 21 persons attempting suicide and 8 (44.4%) of 18 who had a psychiatric hospitalization were symptomatic. A total of 11 (84.6%) of 13 asymptomatic persons who experienced a CE during the first year after HD predictive testing received an increased-risk result. Factors associated with an increased risk of a CE included (a) a psychiatric history
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| 10. |
- Asplund, Kenneth, et al.
(författare)
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Facial Expressions of Patients With Dementia : A Comparison of Two Methods of Interpretation
- 1995
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Ingår i: International psychogeriatrics. - 1041-6102 .- 1741-203X. ; 7:4, s. 527-534
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Tidskriftsartikel (refereegranskat)abstract
- Two methods of interpreting the videotaped facial expressions of four patients with severe dementia of the Alzheimer type were compared. Interpretations of facial expressions performed by means of unstructured naturalistic judgements revealed episodes when the four patients exhibited anger, disgust, happiness, sadness, and surprise. When these episodes were assessed by use of modified version of the Facial Action Coding System, there was, in total, 48% agreement between the two methods. The highest agreement, 98%, occurred for happiness shown by one patient. It was concluded that more emotions could be judged by means of the unstructured naturalistic method, which is based on an awareness of the total situation that facilitates imputing meaning into the patients' cues. It is a difficult task to find a balance between imputing too much meaning into the severely demented patients' sparse and unclear cues and ignoring the possibility that there is some meaning to be interpreted.
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