Biomedical subjects

C Zander

Publications and source records attributed to C Zander.

At least 19 recordsLinked to original sources

PubMed2000

No evidence for long CAG/CTG repeats in families with spastic paraplegia linked to chromosome 2p21-24.

Autosomal dominant familial spastic paraplegia (AD-FSP) is a genetically heterogeneous, neurodegenerative disorder characterized by spasticity and progressive weakness in the lower limbs. Anticipation has been suggested to occur and an association between expanded CAG/CTG repeats and AD-FSP linked to the SPG4 locus (2p21-p24) has been described. In this study, 42 affected individuals from six SPG4 families were screened for expanded CAG/CTG repeats using the repeat expansion detection (RED) method. Large RED products (range 180-240 nucleotides) corresponding in size to repeats at the ERDA1 locus were detected in eight patients and at the CTG 18.1 locus in one patient. The large ERDA1 repeats did not segregate with the disorder within families. Mean age at onset and index of severity were not significantly different between patients with or without expanded RED products. Furthermore, no abnormal proteins were found by Western blot in 15 selected patient samples as compared with controls, using the 1C2 antibody, which detects long polyglutamine stretches. Thus, in contrast to previous reports, our study provides evidence against the hypothesis that a large translated CAG repeat expansion is the basis of SPG4. We propose that mechanisms other than large pathogenic CAG/CTG repeats may account for the disease in the SPG4 families tested here.

Adolescent↗

PubMed1999

Non-invasive characterization of cardiac microvascular disease by nuclear medicine using single-photon emission tomography.

In about 10 to 30% of patients with typical angina undergoing coronary angiography for suspicion of stenotic coronary artery disease angiographically normal coronary arteries are found. Kemp et al. in 1973 coined the term syndrome X to describe this entity. In a substantial portion of these patients pathologic findings in myocardial scintigraphy are present. Sensitivity and specificity of thallium-201 exercise imaging by visual analysis of images in the presence of significant coronary stenosis is 84 and 88%, respectively. Several investigators have reported abnormal results in radionuclide exercise tests in patients with angiographically normal coronary arteries. Some of these results can be explained by myocardial bridging, vasospasm, left or right bundle branch block, hypertrophic cardiomyopathy, or absorption artifacts. In the majority of cases, however, these abnormalities are not sufficient to explain the scintigraphic findings. Formerly often claimed "false positive", recent studies suggest that endothelial dysfunction might be the reason for the observed perfusion defects. When comparing patients with angiographically unobstructed coronary arteries with and without perfusion defects in stress myocardial perfusion imaging, patients with pathological results show a significantly lower increase of coronary flow after intracoronary injection of the endothelial-dependent vasodilator acetylcholine. Endothelial-independent vasodilation, however, is not impaired in these patients. In addition, intracoronary Doppler measurements reveal that perfusion defects in myocardial scintigraphy only occur if coronary blood flow in this perfusion area is significantly reduced. These results suggest that regional endothelial dysfunction may cause hypoperfusion in myocardial perfusion imaging and underline the important role of the microcirculation in the distribution of radiotracers. Another striking scintigraphic pattern in patients with microvascular angina is the high incidence of reverse redistribution. These perfusion defects, apparent in images obtained 4 hours after exercise stress testing, often cannot be assigned to the perfusion territory of one of the major epicardial vessels. This results in a marked inhomogeneous radionuclide distribution pattern in resting images. The inhomogeneity is associated with a significant reduced resting coronary flow velocity in these patients. As histologically confirmed microvessel disease is often accompanied by slow-flow phenomenon reflecting decreased resting flow velocity, the results suggest that the inhomogeneous perfusion pattern is caused by microvascular dysfunction. Furthermore, the heterogeneity of nuclide distribution supports the hypothesis that endothelial function is not homogeneous in the entire myocardial microcirculation, but varies considerably. In conclusion, microvascular dysfunction by itself seems to cause regional myocardial hypoperfusion, as documented by myocardial scintigraphy. When interpreting pathological scintigraphic results in patients without significant epicardial stenosis, true blood flow and myocardial perfusion abnormalities must be assumed.

Animals↗

PubMed1999

Treatment of patients with low-risk myelodysplastic syndromes using a combination of all-trans retinoic acid, interferon alpha, and granulocyte colony-stimulating factor.

Used as single agents, ATRA, G-CSF, and IFN-alpha have shown a moderate benefit in patients with low-risk MDS, with a response rate of 10%. The aim of the present study was to evaluate the efficacy of a combination of these agents. The effect on hemoglobin (Hb), platelets, and absolute neutrophil count (ANC), as well as on transfusion frequency, was examined in 25 patients with MDS (11 RA, four RARS, eight RAEB, two CMML). The median age was 61 years (range 44-81), and the male/female ratio was 14/11. Treatment consisted of ATRA at 25 mg/m2/day p.o. for months 1, 3, 5, 7, 9, and 11, IFN-alpha at 1.5 MIU twice a week s.c. for 52 weeks, and, in patients with initial ANC <500/microl, G-CSF at 100-480 microg daily s.c. according to the degree of ANC. The duration of therapy was scheduled for 12 months. Two patients achieved ongoing CR (+19 months; +16 months), one patient with RA after 3 months and one with CMML after 7 months of treatment. In all patients, the mean ANC increased significantly from 1400+/-200/microl before the start of therapy to 3500+/-600/microl at the end of treatment (p=0.025). In two patients an increase of Hb was observed, and one patient ceased to require transfusions. In an additional patient with RA and 5q-syndrome, the platelet count normalized following administration of ATRA/IFN-alpha, increasing from 89,000/microl to 293,000/microl. The eight RAEB patients were nonresponders. We conclude that therapy with ATRA, IFNalpha, and G-CSF is effective in approximately 35% of low-risk MDS patients (in this study: six of 17) and may induce complete remission in individual cases.

Adult↗

PubMed1998

Anticipation in schizophrenia: no evidence of expanded CAG/CTG repeat sequences in French families and sporadic cases.

A decrease in age of onset of schizophrenia through consecutive family generations (anticipation) has been found in several studies. Anticipation is known to result from expansion of CAG repeats in genes that determine several neurodegenerative disorders. In a previous study we analysed 26 unilineal two-generation French pedigrees and found clinical evidence of anticipation. A 10-year mean reduction in age of onset of schizophrenia was found in the second generation compared with the parental generation. The repeat expansion detection method was used to screen for CAG expansion in 21 of the 26 families with evidence of anticipation for the disease and in 59 sporadic schizophrenics and 59 controls. Comparison of the frequency distributions of CAG/CTG repeat size observed in schizophrenics and controls showed no significant difference, even when we considered familial (P = 0.23) and sporadic (P = 0.25) affected individuals separately. These results do not support the association between long CAG repeats and schizophrenia. However, the possibility that expansions with fewer than 40 repeats are involved in schizophrenia cannot be excluded.

Adult↗

PubMed1998

CAG repeat sequences in bipolar affective disorder: no evidence for association in a French population.

Anticipation has been described in bipolar affective disorder (BPAD). However, there are conflicting results from association studies screening for a link between BPAD and CAG/CTG repeat expansions, the molecular basis of anticipation in several hereditary neurodegenerative disorders. Here, the repeat expansion detection (RED) method was used to screen for CAG repeat expansion in 119 French BPAD patients. Western blotting was also used to search for polyglutamine stretches, encoded by CAG expansion, among proteins, extracted from lymphoblastoid cell lines, from six selected familial cases. Maximum CAG/CTG repeat length did not differ significantly (P = 0.38) between the 119 BPAD patients and the 88 controls included in the study. Several categories of subgroups were used, none of which showed significant association with a long repeat. Nor was a specific protein with an unusually long polyglutamine stretch (lower detection limit, approximately 33 polyglutamines) detected in cell lysates from the familial cases studied. In conclusion, an association between a long CAG/CTG repeat and BPAD in the French population sample studied was not found. Nonetheless, a short repeat (<40 repeats) might still be implicated, and this possibility warrants further study.

Adult↗

PubMed1998

Two commonly expanded CAG/CTG repeat loci: involvement in affective disorders?

An association between bipolar affective disorder and CAG/CTG trinucleotide repeat expansions (TRE) has previously been detected using the repeat expansion detection (RED) method. Here we report that 89% of RED products (CAG/CTG repeats) > 120 nt (n = 202) detected in affective disorder patients as well as unaffected family members and controls correlate with expansions at two repeat loci, ERDA1 on chromosome 17q21.3 and CTG18.1 on 18q21.1. In a set of patients and controls in which we had previously found a significant difference in RED size distribution, the frequency of expansions at the CTG18.1 locus was 13% in bipolar patients (n = 60) and 5% in controls (n = 114) (P < 0.07) with a significantly different size distribution (P < 0.03). A second set of patients were ascertained from 14 affective disorder families showing anticipation. Twelve of the families had members with RED products > 120 nt. The RED product distribution was significantly different (P < 0.0007) between affected (n = 53) and unaffected (n = 123) offspring. Using PCR, a higher frequency (P < 0.04) of CTG18.1 expansions as well as a different (P < 0.02) repeat size distribution was seen between affected and unaffected offspring. In addition, a negative correlation between RED product size and the age-of-onset could be seen in affected offspring (rs = -0.3, P = 0.05, n = 43). This effect was due to an earlier onset in individuals with long CTG18.1 expansions. No difference in ERDA1 expansion frequency was seen either between bipolar patients (35%, n = 60) and matched controls (29%, n = 114), or between affected and unaffected offspring in the families. We conclude that expanded alleles at the CTG18.1 locus confers an odds ratio of 2.6-2.8 and may thus act as a vulnerability factor for affective disorder, while the ERDA1 locus seems unrelated to disease.

Bipolar Disorder↗

PubMed1998

Multivariate analysis of factors influencing repeat expansion detection.

Repeat expansion detection (RED) is a powerful tool for detection of expanded repeat sequences in the genome. In RED, DNA serves as a template for a repeat-specific oligonucleotide. A thermostable ligase is used to ligate oligonucleotides that have annealed at adjacent positions, creating multimers in a thermal cycling procedure. The products are visualized after gel electrophoresis, transfered to a membrane and subsequently hybridized. Multiple linear regression (MLR) and partial least square (PLS) techniques were used to reveal the most influential factors in the amplification reaction and to identify possible interacting factors. Ligation temperature proved to be the most important factor in the reaction: Temperatures far below the melting point of the oligonucleotide increased the yield considerably. Higher cycle number resulted in a continuous rise in intensity, indicating that the ligase remained active even after 700 cycles or 12 hr of cycling. In addition, the concentration of ligase was found to be important. Using optimal parameters, a 5.5- and 3.2-fold increase in the yield of 180- and 360-nucleotide products respectively was obtained. The improved sensitivity makes the method more robust and facilitates detection of repeat expansions. This improvement may be particularly useful in development of RED for diagnostic purposes as well as for nonradioactive detection of RED products. Based on these results, a new protocol for the RED method was developed taking into account the risk of introducing artifacts with increased enzyme concentrations and lowered annealing temperatures.

DNA↗

PubMed1998

[Results of selective goiter resection in functional autonomy].

In the period from 1989 to 1994 a surgical treatment of toxic nodular goiter was performed in 145 patients. An unifocal autonomous adenoma occurred in 69 cases, a multifocal disease 76 times. The operative strategy consisted in a bilateral resection 105 times, and unilateral resection 29 times. An excision of a single node was carried out in ten cases. In one operation a hemithyroidectomy on one side and a subtotal resection of the other lobe was done. In May 1996 an interrogation about the current thyroid function was performed. In 105 (72.4%) patients a re-evaluation was possible. Concerning the postoperative therapy for prevention of recurrent hyperthyroidism or goiter growth, 84 patients (80%) had been treated with thyroxin and/or iodine. Under this therapy, after a mean period of 36 months 94 patients (89.5%) were clinically euthyroid. Nine patients (8.6%) were hypothyroid. Two patients developed a recurrent hyperthyroidism. Both of them belonged to the group of patients with multifocal autonomies, and both had been treated with thyroxin postoperatively. In one case, recurrent goiter growth occurred that did not need a therapeutic intervention. This patient as well had been treated for a multinodular goiter originally. She had not been taking a specific medication postoperatively. We conclude that a functional resection of autonomic tissue in nodular goiters is efficient in controlling the thyroid metabolism. A medical prophylaxis was not able to prevent recurrent hyperthyroidism in two cases.

Female↗

PubMed1997

Expanded trinucleotide CAG repeats in families with bipolar affective disorder.

Clinical anticipation has been reported in bipolar affective disorder (BPAD). The hypothesis that expanded trinucleotide repeats are related to anticipation and transmission pattern in families with bipolar affective disorder is tested in this study. Eighty-seven two-generation pairs of patients recruited from 29 bipolar families were analyzed. The repeat expansion detection method was used to detect CAG repeat expansions between successive generations. Significant changes in age at onset and episode frequency in successive generations were observed. Mean trinucleotide CAG repeat length between parental and offspring generation significantly increased when the phenotype increased in severity, i.e., changed from major depression, single episode or unipolar recurrent depression to BPAD. A parent-of-origin effect was also observed with a significant increase in median length CAG between G1 and G2 with maternal inheritance. This increase was observed notably in female offspring. Our findings indicate for the first time that expansion of CAG repeat length could explain the clinical observation of anticipation in families with BPAD. These results provide further support for expanded trinucleotide repeat sequences as risk factors in major affective disorders.

Adult↗

PubMed1997

Value of diuresis renography in the post-natal period of assumed physiological renal immaturity.

The aim of this study was to determine if it is possible to exclude renal obstruction using diuresis renography in the first 6 weeks of life (the period of physiological renal immaturity), thus avoiding unnecessary invasive procedures, such as the Whitaker test or surgery. Diuresis renography with 123I-hippuran was performed in 27 patients aged less than 6 weeks and in 50 older children who acted as a reference group (age 6 weeks to 1 year, n = 28; age 1-10 years, n = 22). All 27 patients had significant dilatation of the pelvicalyceal system on ultrasonography. Renal curves were evaluated by mathematical curve characteristics (split renal function, counts, T-max, etc.) as the visual grade of obstruction. Whole-kidney regions of interest were defined on images summed over 30 min; renal parenchyma on images summed over 5 min. The renal curves of 18/27 patients indicated tracer accumulation and led to frusemide administration. Only two patients showed no significant response to frusemide and had to be further investigated by the Whitaker test. The frequency of kidneys with no response to frusemide revealed no significant differences in the three groups. Whole-kidney evaluation resulted in an overestimation of obstruction in 9/150 kidneys, which matches the lower correlation to the DMSA separation values for this method of evaluation. In contrast with the literature, significant post-renal obstruction can be excluded by diuresis renography in most cases in spite of renal immaturity and can help to avoid invasive procedures.

Child↗

PubMed1997

Oculopharyngeal muscular dystrophy (OPMD)--report and genetic studies of an Australian kindred.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant disease. Due to a founder effect, it is most commonly found in the French Canadian population. The gene has recently been mapped to chromosome 14q11.2-q13 in some of these families. Here we report an Australian kindred of German descent with OPMD. Linkage analysis supports its locus to chromosome 14q. Repeat expansion studies were also carried out, but a CAG trinucleotide repeat expansion detected did not cosegregate with the disease. We conclude that there is no evidence of genetic heterogeneity or involvement of repeat expansion in OPMD.

Australia↗

PubMed1997

SPECT-evaluation of the monoamine uptake site ligand [123I](1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I]beta-CIT) in untreated patients with suspicion of Parkinson disease.

BACKGROUND: For a few years, data on SPECT-imaging of dopamine transporters with the cocaine derivate [123I](1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I] beta-CIT) have been reported mostly in healthy subjects or animals. This study reflects our preliminary results with SPECT-imaging of dopamine transporters using the cocaine analogue 123-beta-CIT in patients with untreated (de novo) parkinsonism. METHODS: In 33 patients with clinical suspicion of Parkinson disease and 5 healthy controls, SPECT-imaging of dopamine transporters was performed 1, 4, and 24 hours after injection of 180 MBq of 123I-beta-CIT, which was generated by iododestannylation. None of the patients or controls had been treated before with neuroleptical drugs or any other pharmaceuticals with known binding to the dopamine transporters. Clinical symptoms were staged by the scales Hoehn-Yahr (HYS), Unified Parkinson Disease Rating Scale (UPDRS), and the self-rating scale of Beck depression inventory (BDI). For evaluation, striatal/cerebellar ratios were calculated to every time point. RESULTS: Significant correlations of 123I-beta-CIT uptake could be stated compared to UPDRS, HYS, and BDI values (Spearman correlation, p < 0.05). The symptoms of rigor and akinesia showed a significant correlation with the beta-CIT uptake, whereas the symptom of tremor failed, which may be caused by the location of tremor symptoms out of the striatum. Comparing the controls, a significant (p < 0.01) decrease of tracer uptake in parkinsonian patients is stated on the images at 24 hours p.i. In our patients, tracer uptake does not depend significantly on duration of disease and age. CONCLUSION: 123I-beta-CIT seems to be a promising tool in imaging of untreated parkinsonian patient.

Adult↗

PubMed1996

Radial cortical and trabecular bone densities of men and women standardized with the European Forearm Phantom.

We previously showed that it is possible to cross-calibrate peripheral bone densitometers using the European Spine Phantom (ESP). We have now performed a multinational study of cross-calibrated radius bone density based on normal subjects of both sexes in eight European centers. Six centers were equipped with machines made by Scanco or Stratec for determining distal radial trabecular bone density by quantitative computed tomography (QCT) and two were equipped with Lunar SP2 single photon absorptiometry (SPA) equipment for measuring midshaft cortical bone density. Subjects recruited ranged from 20 to over 80 years of age. Over one hundred and fifteen men were studied by QCT and a different cohort of 104 men were studied with SPA; the equivalent figures for women were 235 and 123. Reference ranges were derived for bone density against age for each of the four groups, and their applicability is discussed in relation to between-center differences in the results obtained. There were insignificant differences (P > 0.05 with Bonferroni correction) between centers in the values obtained by QCT in the different populations. However, there were considerably larger and highly statistically significant differences between midshaft cortical bone density values of about 10% of overall means between subjects from eastern Finland and central Belgium (P < 0.001), with higher Finnish values. Women had considerably lower radial trabecular bone density values than men at all ages, a result that differentiates the radius from the spine. This sex difference widened after menopause. These results have important implications for understanding the contribution of bone density to the differential risk of Colles' fracture in the two sexes and suggest that further work is needed to establish young normal reference ranges for radial bone density in Europe.

Absorptiometry, Photon↗

PubMed1996

Improved multilineage response of hematopoiesis in patients with myelodysplastic syndromes to a combination therapy with all-trans-retinoic acid, granulocyte colony-stimulating factor, erythropoietin and alpha-tocopherol.

Differentiation induction therapy is being tested in myelodysplastic syndromes to ameliorate maturation defects and to restore normal hematopoietic function. To this end, 17 patients (eight with refractory anemia, two with refractory anemia and ring sideroblasts, and seven with refractory anemia and excess of blast cells) were treated with a combination of all-trans-retinoic acid (ATRA), granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and alpha-tocopherol for durations of 8-16 weeks. Absolute neutrophil counts increased in all patients; platelet counts increased in five patients with discontinuation of transfusion needs in two of four transfusion-dependent patients. Stimulation of erythropoiesis was seen in eight patients with an increase in hemoglobin concentration in three, a discontinuation of transfusion requirements in another three, and a significant increase in reticulocyte counts as the only parameter in two patients. Clinically important multilineage responses with increases of hemoglobin levels or discontinuation of transfusion needs were thus seen in six patients (35.3%) with three patients having a trilineage response. Serum erythropoietin concentrations did not differ significantly between responders and nonresponders, but the erythroid response was accompanied by a rise in the serum transferrin receptor levels. In the bone marrow, the myeloid-to-erythroid ratio and the maturation index of myeloid cells increased during therapy, while the percentage of blast cells did not change. Cytogenetic analysis demonstrated the persistence of the abnormal clones. Prior to therapy, nonresponders had a significantly higher serum TNF level than responders. Serum concentrations of TNF-alpha and soluble TNF-alpha receptor significantly increased during therapy, but mainly in the patients without an erythroid and platelet response. Soluble IL-2 receptor and soluble ICAM-1 concentrations both increased. This pilot study demonstrates that treatment with ATRA/G-CSF/EPO/tocopherol is well tolerated, leading to normalization of neutrophil counts in most, and to improvement of platelets and red blood cells in a significant subgroup of patients.

Adult↗

PubMed1996

Use of various diagnostic methods in a patient with Gaucher disease type I.

A series of plain radiographs, bone scans, bone marrow scans, and MRIs is reported in a patient with Gaucher disease type I, in whom two episodes of acute bone crisis developed during a 6-year period of follow-up. Acute bone crisis and global indolent bone marrow displacement could both be assessed by bone marrow scintigraphy, whereas MRI could better clarify the corti-comedullary alteration after bone infarction. Thus, MRI and bone marrow scintigraphy could be used as complementary imaging methods in the management of patients with Gaucher disease.

Acute Disease↗

PubMed1996

An expanded CAG repeat sequence in spinocerebellar ataxia type 7.

Expanded CAG repeat sequences have been identified in the coding region of genes mutated in several neurodegenerative disorders, including spinocerebellar ataxia type 1 and Machado-Joseph disease. In all disorders described to date the CAG expansion codes for an elongated polyglutamine chain. An increased polyglutamine chain size leads to a more severe disease, thus correlating with the genetic anticipation seen in repeat expansion disorders. Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant spinocerebellar ataxia with anticipation and a progressive degeneration of the cerebellar cortex. Using repeat expansion detection (RED), a method in which a thermostable ligase is used to detect repeat expansions directly from genomic DNA, we have analyzed 8 SCA7 families for the presence of CAG repeat expansions. RED products of 150-240 bp were found in all affected individuals and found to cosegregate with the disease (P < 0.000001, n = 66), indicating strongly that a CAG expansion is the cause of SCA7. On the basis of a previously established correlation between RED product sizes and actual repeat sizes in Machado-Joseph disease, we were able to estimate the average expansion size in SCA7 to be 64 CAG copies.

Chromosome Mapping↗

PubMed1996

Mutation detection in Machado-Joseph disease using repeat expansion detection.

BACKGROUND: Several neurological disorders have recently been explained through the discovery of expanded DNA repeat sequences. Among these is Machado-Joseph disease, one of the most common spinocerebellar ataxias (MJD/SCA3), caused by a CAG repeat expansion on chromosome 14. A useful way of detecting repeat sequence mutations is offered by the repeat expansion detection method (RED), in which a thermostable ligase is used to detect repeat expansions directly from genomic DNA. We have used RED to detect CAG expansions in families with either MJD/SCA3 or with previously uncharacterized spinocerebellar ataxia (SCA). MATERIALS AND METHODS: Five MJD/SCA3 families and one SCA family where linkage to SCA1-5 had been excluded were analyzed by RED and polymerase chain reaction (PCR). RESULTS: An expansion represented by RED products of 180-270 bp segregated with MJD/SCA3 (p < 0.00001) in five families (n = 60) and PCR products corresponding to 66-80 repeat copies were observed in all affected individuals. We also detected a 210-bp RED product segregating with disease (p < 0.01) in a non-SCA1-5 family (n = 16), suggesting involvement of a CAG expansion in the pathophysiology. PCR analysis subsequently revealed an elongated MJD/SCA3 allele in all affected family members. CONCLUSIONS: RED products detected in Machado-Joseph disease families correlated with elongated PCR products at the MJD/SCA3 locus. We demonstrate the added usefulness of RED in detecting repeat expansions in disorders where linkage is complicated by phenotyping problems in gradually developing adult-onset disorders, as in the non-SCA1-5 family examined. The RED method is informative without any knowledge of flanking sequences. This is particularly useful when studying diseases where the mutated gene is unknown. We conclude that RED is a reliable method for analyzing expanded repeat sequences in the genome.

Alleles↗

PubMed1995

Detection of expanded CAG repeats in bipolar affective disorder using the repeat expansion detection (RED) method.

Genetic factors are of major aetiological importance in Bipolar Affective Disorder (BPAD type I and II). The exact mode of inheritance of BPAD is unknown, but the recent demonstration of anticipation suggests that dynamic mutations could be involved in the clinical expression of the disease. We have used the repeat expansion detection (RED) method to test whether the anticipation in BPAD could be explained by the presence of expanded trinucleotide repeat sequences. Using a (CTG)10 oligonucleotide a significantly higher number of expanded CAG repeats were found in the genomic DNA of two independent samples of unrelated BPAD patients of Swedish and Belgian ancestry as compared with normal controls. The difference in repeat number was more consistent if data of the two samples of patients was pooled. In this study a CAG trinucleotide repeat expansion was associated for the first time with a major psychiatric disorder. It is possible that the CAG trinucleotide repeat expansion is involved in the clinical expression of BPAD and that it is the molecular basis explaining the phenomenon of anticipation observed in this disorder.

Aged↗