PubMed Health⌕ Search

Biomedical subjects

L J Schut

Publications and source records attributed to L J Schut.

18 recordsLinked to original sources
PubMed1995

Spinocerebellar ataxia type 1 and Machado-Joseph disease: incidence of CAG expansions among adult-onset ataxia patients from 311 families with dominant, recessive, or sporadic ataxia.

The ataxias are a complex group of diseases with both environmental and genetic causes. Among the autosomal dominant forms of ataxia the genes for two, spinocerebellar ataxia type 1 (SCA1) and Machado-Joseph disease (MJD), have been isolated. In both of these disorders the molecular basis of disease is the expansion of an unstable CAG trinucleotide repeat. To assess the frequency of the SCA1 and MJD trinucleotide repeat expansions among individuals diagnosed with ataxia we have collected DNA from individuals representing 311 families with adult-onset ataxia of unknown etiology and screened these samples for trinucleotide repeat expansions within the SCA1 and MJD genes. Within this group there are 149 families with dominantly inherited ataxia. Of these, 3% had SCA1 trinucleotide repeat expansions, whereas 21% were positive for the MJD trinucleotide expansion. Thus, together SCA1 and MJD represent 24% of the autosomal dominant ataxias in our group, and the frequency of MJD is substantially greater than that of SCA1. For the 57 patients with MJD trinucleotide repeat expansions, a strong inverse correlation between CAG repeat size and age at onset was observed (r = -.838). Among the MJD patients, the normal and affected ranges of CAG repeat size are 14-40 and 68-82 repeats, respectively. For SCA1 the normal and affected ranges are much closer, containing 19-38 and 40-81 CAG repeats, respectively.

Adult↗
PubMed1994

Knowledge of genetics and attitudes toward genetic testing in two hereditary ataxia (SCA 1) kindreds.

Molecular genetic predictive or prenatal genetic testing is now possible in families with one form of adult-onset, autosomal dominant ataxia (SCA 1). Before the SCA 1 gene was isolated, we began a study of the knowledge of genetics, the perception of the disease, and the intended use of genetic testing among members of two large SCA 1 kindreds. Questionnaires were sent to 210 consenting affected, at-risk, and spouse members of two SCA 1 kindreds; data from the 117 respondents were analyzed on a personal computer. Sixty-nine percent of respondents thought predictive testing (by genetic linkage) should be made available immediately, and 42% thought prenatal testing should be made available. The kindreds differed in several important aspects: knowledge of genetic concepts, family size, and anticipated emotional responses to genetic testing. No respondent had obtained individualized genetic counseling. There is moderate interest in genetic testing for this fatal neurodegenerative disease of adulthood. Members of our kindreds have not received genetic counseling outside of the research setting. Finally, factors specific to a particular kindred may influence or predict individual responses to genetic testing.

Adult↗
PubMed1994

Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11.

Autosomal dominant ataxias are a genetically heterogeneous group of disorders for which spinocerebellar ataxia (SCA) loci on chromosomes 6p, 12q, 14q and 16q have been reported. We have examined 170 individuals (56 of whom were affected) from a previously unreported ten-generation kindred with a dominant ataxia that is clinically and genetically distinct from those previously mapped. The family has two major branches which both descend from the paternal grandparents of President Abraham Lincoln. Among those examined, 56 individuals have a generally non-life threatening cerebellar ataxia. Disease onset varies from 10-68 years and anticipation is evident. We have mapped this gene, spinocerebellar ataxia type 5 (SCA5), to the centromeric region of chromosome 11.

Adolescent↗
PubMed1994

Molecular and clinical correlations in spinocerebellar ataxia type I: evidence for familial effects on the age at onset.

The spinocerebellar ataxias are a group of debilitating neurodegenerative diseases for which a clinical classification system has proved unreliable. We have recently isolated the gene for spinocerebellar ataxia type 1 (SCA1) and have shown that the disease is caused by an expanded, unstable, CAG trinucleotide repeat within an expressed gene. Normal alleles have a size range of 19-36 repeats, while SCA1 alleles have 42-81 repeats. In this study, we examined the frequency and variability of the SCA1 repeat expansion in 87 kindreds with diverse ethnic backgrounds and dominantly inherited ataxia. All nine families for which linkage to the SCA1 region of 6p had previously been established showed repeat expansion, while 3 of the remaining 78 showed a similar abnormality. For 113 patients from the families with repeat expansion, inverse correlations between CAG repeat size and both age at onset and disease duration were observed. Repeat size accounted for 66% of the variation in age at onset in these patients. After correction for repeat size, interfamilial differences in age at onset remained significant, suggesting that additional genetic factors affect the expression of the SCA1 gene product.

Adolescent↗
PubMed1992

Autosomal dominant spinocerebellar ataxia: locus heterogeneity in a Nebraska kindred.

SCA1 is an adult-onset autosomal dominant ataxia that is genetically linked to loci on chromosome 6p. A highly informative GT-repeat marker, D6S89, has been closely linked to the SCA1 locus in five large kindreds. We have used this marker to perform linkage analysis in a smaller autosomal dominant ataxia family consisting of five generations designated as the Nebraska kindred. This kindred includes 33 affected (12 living) and 40 first-generation at-risk individuals. We examined eight affected individuals; all had gait and limb ataxia. We analyzed the D6S89 locus by the polymerase chain reaction. Based on the analysis of 31 individuals from this kindred, we statistically excluded linkage to D6S89 for moderate-to-tight linkage (less than 11% recombination). These data clearly demonstrate genetic heterogeneity among the autosomal dominant ataxias. In addition, we obtained linkage data for HLA-A and SCA1 in this kindred. Comparison of HLA-A with D6S89 shows the latter marker to be more powerful. Use of D6S89 and other highly polymorphic markers in this region will greatly facilitate genetic classification of ataxias and make presymptomatic diagnosis of SCA1 feasible.

Adolescent↗
PubMed1991

Spinocerebellar ataxia: multipoint linkage analysis of genes associated with the disease locus.

Spinocerebellar ataxia (SCA) was studied in a seven-generation (Schut-Swier) kindred using linkage analysis to localize further the autosomal dominant, HLA-linked, disease-producing SCA1 locus relative to four other loci that map to the short arm of human chromosome 6. Genotypes for each locus were determined in as many individuals as possible from a total of 162 affected and unaffected family members that were studied. A maximum pairwise lod score of 8.52 (theta m = 0.10, theta f = 0.22) for linkage between SCA1 and HLA-A was observed. Multipoint linkage analyses for the SCA1, HLA-A, F13A, D6S7, and GLO1 loci revealed that the SCA1 locus is most probably located telomeric to HLA-A, with a likely location between HLA-A and F13A.

Chromosome Mapping↗
PubMed1991

Localization of the autosomal dominant HLA-linked spinocerebellar ataxia (SCA1) locus, in two kindreds, within an 8-cM subregion of chromosome 6p.

Two large kindreds with HLA-linked, autosomal dominant spinocerebellar ataxia (SCA1) were examined with markers from chromosome 6p to determine the location of the SCA1 locus. Results of the three-point analysis between the markers HLA-A, SCA1, and F13A overwhelmingly favor the conclusion that SCA1 is located distal of HLA and proximal of F13A. In addition, our data strongly support the conclusion that SCA1 lies centromeric and genetically very close to the highly informative D6S89 marker within the 8-cM chromosomal segment flanked by the D6S88 and D6S89 markers. In the two kindreds, one recombinant was observed between D6S89 and SCA1, resulting in a recombination fraction of .014 between the two loci.

Adolescent↗
PubMed1989

The spectrum of imaging and neuropsychological findings in Pick's disease.

To seek improved methods for the diagnosis of Pick's disease, we reviewed imaging studies of four women and two men (ages 48 to 65 years at onset) and psychometric testing of three of them with autopsy or biopsy-proved Pick's. The presence of Pick bodies was required for the diagnosis. Seven patients with biopsy-proved Alzheimer's disease served as a comparison group. In the Pick's patients, CT in five of six showed marked frontal pole or temporal pole atrophy, which clearly differed from the pattern of cerebral atrophy seen in the Alzheimer's patients. Psychometric testing showed performance patterns that tended to differ from those of the Alzheimer's patients in that recent memory was relatively preserved despite marked impairment of executive functions. The distinctive psychometric pattern in the Pick's patients was evanescent, however. Thus, there were imaging and psychometric findings of potential diagnostic value for Pick's disease, but, for different reasons, they were imperfect.

Aged↗
PubMed1988

The coexistence and differentiation of late onset Huntington's disease and Alzheimer's disease. A case report and review of the literature.

The case report presented is clinically compatible with late onset HD. The diagnosis was initially obscured by a lack of family history due to the early death of both parents and siblings. The presence of symptoms at the age of 59 in one offspring is consistent with the intrafamilial transmission of late onset HD disease. The early neuropsychometric data were consistent with the cognitive changes of HD, particularly with the loss of higher cognitive functions, memory and the relative decline in the performance IQ with the preservation of language skills. The psychiatric symptoms of emotional lability and apathy were also congruent with the diagnosis of HD. The atypical features of this patient's course, including progressively severe dementia, seizures and rigidity, may have provided clinical clues to the coexistence of both AD and HD. The absence of caudate atrophy on serial CT scans in this patient, although inconsistent with the gross findings reported on postmortem exam, perhaps could be explained by the 3 1/2-year interval between the last CT scan and death. Further, it has been noted previously that pathological changes tend to lag behind the clinical manifestations of the disease. The pathologic findings on autopsy were confirmatory for the presence of both AD and HD in this patient. Genetic counseling for this family is now most appropriate.

Age Factors↗
PubMed1988

Dementia following stroke.

Strokes can be due to ischemic or hemorrhagic vascular disorders. Ischemic strokes outnumber hemorrhagic strokes approximately 4:1. Although the mode of presentation and pathophysiology are different in the two conditions, the outcome is really dependent on the extent and location of brain injury. A CT scan helps in this regard and reveals surgically correctable lesions such as a subdural hematoma or normal pressure hydrocephalus. Effective rehabilitation of the stroke patient is dependent on motivation and cognitive ability even more than on remaining motor or sensory function. A team approach to assessment provides the opportunity to make an accurate appraisal of a patient's current level of functioning and an estimate of premorbid capabilities. A thorough review of the history, complete neurologic examination, mental status testing, and laboratory and radiographic data should be obtained by the treating physician. Neuropsychologic testing, speech and language evaluation, ADL assessment, nursing observations, and psychiatric consultation round off the attempts to fully learn the limitations and strengths that characterize the patient. The value in assessing cognitive abilities after a stroke should be obvious. Not only is motivation necessary, but the patient must comprehend the purpose of the rehabilitation process. Goal-setting is a combined effort of the patient and the rehabilitation team. If a patient has limited understanding and faulty memory, the efforts may be wasted. The presence of acute confusion or delirium may delay rehabilitation efforts, but the etiology may be readily treatable. When there is strong suspicion of a degenerative dementia such as Alzheimer's disease, the expectations are lowered. Occasionally, the problem is a mixed dementia in which instance the prognosis is poor. When there is evidence for multi-infarct dementia, there is a possibility for cognitive improvement when medical problems such as hypertension and embolization are treated. Much can be done for one who has limited and focal cerebral damage provided there is adequate comprehension and ability to compensate for disability.

Aged↗
PubMed1987

Changes in vitamin E concentration in red blood cells and plasma of patients with olivopontocerebellar ataxia within the Schut-Swier kindred.

Many reports have documented the importance of vitamin E for the function of the nervous system, especially of the cerebellum. Therefore, we studied the concentrations of vitamin E in the blood plasma and red blood cells of patients with a hereditary form of olivopontocerebellar ataxia. The concentrations of alpha tocopherol (the principal biologically-active form of vitamin E) in the plasma and red cells of the ataxic subjects were significantly lower than those of unaffected, close relatives as well as unrelated control subjects. Total lipids, cholesterol, triglycerides and lipoproteins in the serum of the ataxia group were all within normal range. The results suggest that this specific type of familial ataxia is associated with a rare and isolated abnormality in vitamin E and/or antioxidant metabolism. The vast majority of previous reports of lower blood concentrations or deficiency of vitamin E in children or adults were also associated with deficits in the absorption of lipids or abnormalities in serum lipids and lipoproteins.

Adult↗
PubMed1987

Abnormal ocular motor function predicts clinical diagnosis of familial ataxia.

Ocular motor performance was significantly impaired in familial ataxia patients as compared with normal controls. Ataxic patients showed prolonged saccadic latencies, longer saccadic refixation times, reduced visual tracking performance, and increased hypermetria. Cutoff values were derived and applied to 15 subjects at risk for developing familial ataxia. Three of 15 showed abnormal values in three or more of four categories of ocular motor performance. Within 3 years, all three subjects were diagnosed on clinical grounds as having familial ataxia. We conclude that ocular motor performance is impaired in familial ataxia and may prove useful for earlier diagnosis.

Eye Movements↗
PubMed1984

Spinocerebellar ataxia in a large kindred: age at onset, reproduction, and genetic linkage studies.

We studied a large kindred with autosomal dominant spinocerebellar ataxia (SCA) to assess reproductive performance, the impact of genetic counseling, and linkage relationships of the SCA locus. Reproduction was not lower in those with SCA than in unaffected sibs or first cousins. Genetic counseling reduced reproduction during the risk period for development of SCA. Given autosomal dominant transmission of a single gene, we found strong evidence that the locus for SCA in this kindred is linked to the HLA loci.

Adolescent↗
PubMed1983

Efficacy trial of heat-inactivated hepatitis B vaccine (CLB) in male homosexuals in the Netherlands.

The efficacy of a heat-inactivated hepatitis B virus (HBV) vaccine, containing 3 micrograms-HBsAg, was studied among a group of 800 susceptible homosexual men. The trial was conducted randomized, placebo-controlled and double blind. At the trial end point (21.5 months) the attack-rate for all HBV infections together was 4.8% among vaccinees and 23.8% among the placebos (p less than 0.0001). Four months after the first injection 89% of the vaccinees had formed anti-HBs and this percentage declined only slightly during the follow-up period. Maximum titers were reached 5 months after the first vaccination. None of the vaccinees who responded to the vaccine with anti-HBs greater than or equal to 1 mIU/ml developed a HBsAg positive infection. The vaccine had no serious side-effects.

Clinical Trials as Topic↗