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Marina Svetel

Publications and source records attributed to Marina Svetel.

At least 19 recordsLinked to original sources
PubMed2006

Intrafamilial phenotypic and genetic heterogeneity of dystonia.

Most cases of early-onset primary torsion dystonia are caused by the same 3-bp (GAG) deletion in the DYT1 gene. We describe a large Serbian family with significant intrafamilial variability of the DYT1 phenotype, from asymptomatic carrier status to late-onset focal, and generalized jerky dystonia. Seven mutation carriers (six proven by direct analysis and one by inferred haplotype) were identified, but only two of them were affected by dystonia (penetrance reduced to 29%). In addition, three GAG-deletion-negative family members also developed dystonia (two multifocal dystonia and one torticollis), suggesting that their involuntary movements are due to some other etiological factor(s) (i.e., another dystonia gene), or may be psychogenic.

Adult↗
PubMed2006

Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation.

OBJECTIVE: Neurodegeneration with brain iron accumulation (NBIA) is a group of disorders characterized by magnetic resonance imaging (MRI) changes in basal ganglia. Both missense and nonsense mutations have been found in such patients in a gene encoding the mitochondrial pantothenate kinase (PANK2). METHODS: We completed a mutation screen in 72 patients with the diagnosis NBIA based on clinical findings and radiological imaging. The entire coding region of the PANK2 gene (20p12.3) was investigated for point mutations and deletions. RESULTS: We uncovered both mutant alleles in 48 patients. Deletions accounted for 4% of mutated alleles. Patients with two loss-of-function alleles (n = 11) displayed symptoms always at an early stage of life. In the presence of missense mutations (n = 37), the age of onset correlated with residual activity of the pantothenate kinase. Progression of disease measured by loss of ambulation was variable in both groups. We did not observe a strict correlation between the eye-of-the-tiger sign and PANK2 mutations. In 24 patients, no PANK2 mutation was identified. INTERPRETATION: Deletion screening of PANK2 should be part of the diagnostic spectrum. Factors other than enzymatic residual activity are determining the course of disease. There are strong arguments in favor of locus heterogeneity.

Adolescent↗
PubMed2006

Frequency analysis and clinical characterization of different types of spinocerebellar ataxia in Serbian patients.

The relative frequencies of different spinocerebellar ataxias (SCAs) vary widely among different ethnic groups, presumably due to a founder effect. We investigated the relative prevalence of SCA1-3, 6-8, 12, 17; dentate-rubro-pallidoluysian atrophy; and Friedreich's ataxia (FRDA) in Serbian patients with adult-onset (>20 years of age) hereditary and sporadic SCAs, and compared clinical features of patients with genetically confirmed SCAs. A total of 108 patients from 54 families (38 apparently dominant [ADCA] and 16 apparently recessive) with adult-onset hereditary ataxia and 75 apparently sporadic patients were assessed. Of 38 families with ADCA, 13 (34%) were positive for an expansion in an SCA1 and 5 families (13%) for an expansion in an SCA2 allele. In 20 families (53%), no expansions have been identified in any of the analyzed genes. Gaze palsy, spasticity, and hyperreflexia were significantly more common in SCA1, whereas slow saccades, hypotonia, hyporeflexia, and dystonia prevailed in SCA2 patients. Among the 16 families with an apparently recessive mode of ataxia inheritance, 4 (25%) were identified as having the FRDA mutation. Ataxia-causing mutations were identified in 8 (10.6%) of patients with apparently sporadic adult-onset ataxia.

Adult↗
PubMed2006

Changes in cortical inhibition during task-specific contractions in primary writing tremor patients.

Primary writing tremor (PWT) is a rare disease of unknown pathophysiology. We studied changes in silent period (SP) duration, after transcranial magnetic stimulation (TMS), set at 20% above the motor threshold in 6 PWT patients and 7 healthy control subjects. SP duration was tested during a task-specific act, i.e., writing that induced tremor in all patients in the affected hand (Wr); nonspecific voluntary contraction of intensity, matching that developed during writing (VCWr); and during near maximal voluntary contraction (VCNmax). There were no differences in SP duration during Wr and VCWr contraction on the right affected side or between sides in both PWT patients and control subjects, nor between the groups. However, during VCNmax, SP significantly shortened on both sides in PWT patients, whereas there were no changes in control subjects. Although it appears that inhibitory mechanism are not directly involved in the generation of the tremulous activity, the shortening of SP indicates that central inhibitory mechanisms are affected in PWT patients. Therefore, whereas the underlying pathophysiological mechanisms in PWT and writer's cramp may share common features, the results indicate that PWT is not a variant of focal task-specific dystonia but rather a separate nosological entity.

Adult↗
PubMed2006

Heterozygous PINK1 mutations: a susceptibility factor for Parkinson disease?

PINK1 mutations cause recessively inherited early-onset Parkinson's disease (EOPD). We comprehensively tested 75 Serbian and 17 South Tyrolean EOPD patients for mutations in this gene and found three heterozygous mutation carriers. Two of these patients shared mutations with their affected relatives, further suggesting that heterozygous PINK1 mutations may act as a susceptibility factor for EOPD.

Adolescent↗
PubMed2006

Clinical characteristics of paroxysmal nonkinesigenic dyskinesia in Serbian family with Myofibrillogenesis regulator 1 gene mutation.

The aim of this study was to describe the clinical features of a large Serbian family with paroxysmal nonkinesigenic dyskinesia (PNKD) and one of the two previously described mutations in the Myofibrillogenesis regulator 1 gene (MR-1), which causes an alanine-to-valine substitution at position 9. In 5 examined out of 12 affected family members, attacks of dyskinesias appeared in the first 6 months of life. Both frequency and severity of attacks showed an age-dependent incremental-decremental pattern with a peak between 13 to 15 years of age. They were frequently precipitated by stress, caffeine, fever, hunger, tiredness, as well as abrupt changes in temperature. Three of our patients differentiated two types of attacks: mild (120-180 minutes), with a predominance of functionally insignificant choreoathetoid movements, and severe ( approximately 15-30 minutes), characterized by disabling dystonic and choreic movements of the extremities, trunk, and face. Sleep was the most reliable factor to discontinue an attack. This Serbian family further demonstrates that recurrent MR-1 mutations are associated with PNKD worldwide, which will affect genetic testing.

Adolescent↗
PubMed2006

[Clinical characteristics of multiple system atrophy in serbian population].

BACKGROUND/AIM: Mulstiple system atrophy (MSA) is a neurodegenerative central nervous system disorder, characterized by any combination of extrapyramidal, cerebellar, pyramidal or autonomic disturbance. The aims of our study were to define clinical characteristics of MSA patients in our population, to account for neuroradiological and electrophysiological profile of the disease and to evaluate one-dose levodopa response. METHODS: We have diagnosed 29 patients as MSA, with disease duration from the first symptom 5 years on average on examination. The examinating procedure included an anamnesis and complete neurological investigations, as well as neurootological and neuroradiological examinations. The study included the patients of the Institute of Neurology of the Clinical Center of Serbia in the period of 1996-2001, who completed both clinical and diagnostic criteria for a possible and probable MSA. RESULTS: Autonomic disturbances were documented in 93.1%, whereas extrapyramidal symptoms were seen in additional 89.3% with symmetrical onset in 60%. Levodopa response was poor or moderate. Cerebellar signs were present in 63%, while pyramidal signs occured in 78.7%. There was no a cognitive deterioration (MMSE > 24). CT scan and MRI showed cerebellar and brainstem atrophy, as well as diffuse cortical atrophy. CONCLUSION: Failure of additional diagnostic procedures to distinguish MSA patients required a precise understanding of their clinical specificities. Our results support this statement.

Antiparkinson Agents↗
PubMed2005

Yugoslav HD phenocopies analyzed on the presence of mutations in PrP, ferritin, and Jp-3 genes.

Huntington disease (HD) is a well-defined autosomal dominant neurodegenerative disease caused by CAG repeat expansions in HD gene. There are a significant number of HD cases where this mutation was not found and such cases are named HD-like phenotype (HDL). This article reports 48 patients with HDL phenotype. Patients were analyzed on the presence of mutations in prion (PrP), ferritin and junctophilin-3 (JP-3) genes. None of the patients showed the presence of the mutation in analyzed genes. This could suggest that there is some other gene/genes where the mutation can cause the disease with clinical features of HD.

Brain↗
PubMed2005

[Reversible brain damage following acute poisoning with an organic solvent determined by magnetic resonance].

INTRODUCTION: Acute exposure to the effects of volatile solvents is characterized by the abrupt onset of symptoms and signs of poisoning, and relatively fast recovery in the majority of cases. CASE REPORT: We report a 24-year-old patient with an acute, accidental poisoning with a mixture of volatile organic solvents (most probably toluene, styrene and xylene), which led to the development of upward gaze paresis, diplopia, hemiparesis, ataxic gate, and the late onset truncal ataxia episodes. After 6 weeks, he recovered completely, while his extensive brain MRI lesions in the caudate nuclei, laterobasal putaminal regions, bilateral anterior insular cortex, central midbrain tegmental area) withdrew completely after 4 months. CONCLUSION: Acute toxic encephalopathy should be a part of the differential diagnosis in any patient with acute neurobehavioral and neurological deficit.

Acute Disease↗
PubMed2004

Detection of Parkin (PARK2) and DJ1 (PARK7) mutations in early-onset Parkinson disease: Parkin mutation frequency depends on ethnic origin of patients.

Mutations in the Parkin (PARK2) and the DJ1 (PARK7) gene cause early-onset Parkinson disease (EOPD). We tested 75 Serbian EOPD patients for mutations in both genes by conventional mutational screening (SSCP/dHPLC/sequencing) to detect small sequence alterations and by gene dosage studies (quantitative PCR) to reveal deletions or multiplications of one or more exons. A compound heterozygous Parkin mutation (exon deletion and point mutation; [c.836_972del]+[c.1411C>T]; +1 is first nucleotide of GenBank AB009973.1) was identified in a patient who showed a relatively benign course after a disease onset at 41 years. Another case had a heterozygous exon deletion in DJ1 ([c.253_322del]+[?]) and presented with an age at onset of 45 years and a rapid disease course. In conclusion, Parkin mutations are surprisingly rare in our Serbian EOPD sample, suggesting that the mutation rate depends on the ethnic origin of the patients. Although DJ1 mutations appear to be rare, we confirm their role in EOPD and demonstrate the importance of gene dosage studies.

Adult↗
PubMed2004

Bilateral chorea-ballism associated with hyperthyroidism.

We describe a 50-year-old patient with four episodes of recurrent bilateral chorea-ballism (BCB) and associated hyperthyroidism. Reappearance of BCB, associated with increased serum levels of thyroid hormones and lack of relevant changes on brain computed tomography/magnetic resonance imaging scans, suggested that the involuntary movements were likely due to thyrotoxicosis-induced biochemical changes.

Chorea↗
PubMed2004

Incidence of vascular hemiballism in the population of Belgrade.

Hemiballism is a relatively rare hyperkinetic disorder with unknown incidence. Stroke is the most common cause of hemiballism (vascular hemiballism), responsible for the disorder in 50% to 100% of cases. We studied the incidence of vascular hemiballism in the population of Belgrade (Serbia) 40 years of age or older during the period 1 January 1991 to 31 December 2002. During that time period, 37 patients with hemiballism due to stroke were diagnosed. The annual incidence rates varied from 0.14 to 0.87/100,000 (average 0.45/100,000) of general population.

Adult↗
PubMed2004

Circulating and cerebrospinal fluid ghrelin and leptin: potential role in altered body weight in Huntington's disease.

OBJECTIVE: In addition to neurological impairment, weight loss is a prominent characteristic of Huntington's disease (HD). Neuropathologically, the disease affects the caudate nucleus and the cerebral cortex, and also the hypothalamus. The recently discovered orexigenic hormone of gastric origin, ghrelin and the adipocyte hormone leptin, are two peripherally produced hormones exerting opposite effects on specific populations of hypothalamic neurons that play a key role in regulating energy intake and energy output. The aim of this study was to investigate the possible involvement of cerebrospinal fluid (CSF) and circulating ghrelin and leptin in the regulation of energy balance in patients with HD. METHODS: Twenty healthy normal-weight subjects undergoing orthopedic surgery, and fifteen patients with genetically verified HD, were enrolled in this study. The unified Huntington's disease rating scale (UHDRS) was used to assess clinical course of the disease. Blood samples for hormonal measurements were obtained by venipuncture and in-parallel CSF samples for leptin/ghrelin determination were obtained by lumbar puncture. RESULTS: Patients with HD had increased concentrations of ghrelin in plasma compared with healthy subjects (4523.7+/-563.9 vs 2781.1+/-306.2 pg/ml, P<0.01). On the other hand, patients with HD had decreased concentrations of leptin in plasma compared with healthy subjects (4.8+/-1.6 vs 10.9+/-2.4 ng/ml, P<0.01). The concentrations of CSF ghrelin and CSF leptin were equivalent to values in healthy subjects. No correlation was found between disease duration--and other clinical features of HD--and plasma or CSF leptin/ghrelin levels. In patients with HD, baseline levels of GH, IGF-I, insulin and glucose did not differ from those in healthy subjects. CONCLUSION: High circulating ghrelin and low leptin levels in patients with HD suggest a state of negative energy balance. Early nutritional support of patients with HD is advocated since patients with HD and higher body mass index at presentation have slower progression of the disease.

Adult↗
PubMed2003

Prevalence of primary late-onset focal dystonia in the Belgrade population.

The aim of this cross-sectional study was to estimate the prevalence of different subtypes of idiopathic focal dystonia in the population of Belgrade (Serbia), Yugoslavia. On December 31, 2001, the crude prevalence of all studied types of dystonia (focal, segmental, and multifocal) in Belgrade was 13.6 per 100,000 population (11.8 per 100,000 for men and 15.2 per 100,000 for women). Type-specific prevalence for focal dystonia was 11.2 per 100,000. The prevalence for cervical dystonia, blepharospasm, writer's cramp and laryngeal dystonia were 5.9 per 100,000, 1.9 per 100,000, 1.9 per 100,000, and 1.1 per 100,000, respectively.

Adult↗
PubMed2003

Characterization of the molecular defect in the ATP7B gene in Wilson disease patients from Yugoslavia.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism resulting from the absence or dysfunction of a copper transporting P-type ATPase (ATP7B). Approximately 150 mutations of the ATP7B have been identified to date. In this paper, we report the results of molecular characterization and genotype-phenotype analysis, which we have carried out on 35 patients from Yugoslavia affected by WD. Using single-strand conformational polymorphism (SSCP) followed by direct sequencing, we characterized the molecular defect in 80% of WD chromosomes and found 11 different mutations, three of which are novel. The most common mutations that accounted for the molecular defect in 71.3% of WD chromosomes were H1069Q (48.9%), 2304-2305insC (11.4%), R616Q (5.7%), and A1003T (5.7%). The results produced in this paper indicate that the best strategy for mutation detection in Yugoslavian patients with WD is an SSCP analysis of exons 14, 8, 5, and 13, where most of the defects (73.1%) lie, followed by mutation analysis of the remaining exons in ATP7B in patients in whom the mutation was not detected by the finitial screening. These data can be used to develop straightforward genetic testing in this population or in other countries composed of a genetically mixed population like the United States, where a significant number of immigrants came from Central and Eastern Europe.

Adenosine Triphosphatases↗
PubMed2002

Evidence that paternal expression of the epsilon-sarcoglycan gene accounts for reduced penetrance in myoclonus-dystonia.

Myoclonus-dystonia (M-D) is a movement disorder characterized by rapid muscle contractions and sustained twisting and repetitive movements and has recently been associated with mutations in the epsilon-sarcoglycan gene (SGCE). The mode of inheritance is autosomal dominant with reduced penetrance upon maternal transmission, suggesting a putative maternal imprinting mechanism. We present an apparently sporadic M-D case and two patients from an M-D family with seemingly autosomal recessive inheritance. In both families, we detected an SGCE mutation that was inherited from the patients' clinically unaffected fathers in an autosomal dominant fashion. Whereas, in the first family, RNA expression studies revealed expression of only the mutated allele in affected individuals and expression of the normal allele exclusively in unaffected mutation carriers, the affected individual of the second family expressed both alleles. In addition, we identified differentially methylated regions in the promoter region of the SGCE gene as a characteristic feature of imprinted genes. Using a rare polymorphism in the promoter region in a family unaffected with M-D as a marker, we demonstrated methylation of the maternal allele, in keeping with maternal imprinting of the SGCE gene. Loss of imprinting in the patient with M-D who had biallelic expression of the SGCE gene was associated with partial loss of methylation at several CpG dinucleotides.

Alleles↗
PubMedDate not supplied

Magnetic resonance imaging morphometry of the midbrain in patients with Wilson disease.

In this study, the focus is on midbrain magnetic resonance imaging morphometric measures (transverse diameter of the midbrain peduncle [Tp], transverse diameter of the tegmentum, anteroposterior diameter of the midbrain, interpeduncular distance [IPD], and interpeduncular angle [IPA]) in a group of 47 consecutive patients with neurologic (37 patients) and hepatic (10 patients) forms of Wilson disease (WD). Morphometric measures were significantly different between the group of patients with WD and healthy controls (51 subjects) as well as patients with Parkinson disease (15 patients) and multiple sclerosis (15 patients). Among the studied variables, IPA, Tp, and IPD were particularly useful in differentiating patients from healthy subjects (probability reaching 93%).

Adult↗