Mitochondrial DNA depletion syndromes (MDSs) form a group of autosomal recessive disorders characterized by profoundly decreased mitochondrial DNA copy numbers in affected tissues. Three main clinical presentations are known: myopathic,... more
Mitochondrial DNA depletion syndromes (MDSs) form a group of autosomal recessive disorders characterized by profoundly decreased mitochondrial DNA copy numbers in affected tissues. Three main clinical presentations are known: myopathic, encephalomyopathic and hepatocerebral. The first is associated with mutations in thymidine kinase 2 (TK2) and p53-induced ribonucleotide reductase B subunit (RRM2B); the second with mutations in succinate synthase A (SUCLA2) and B (SUCLG1); the third with mutations in Twinkle (PEO1), pol-γA (POLG1), deoxyguanosine kinase (DGUOK) and MPV17 (MPV17). In this work, we review the MDS-associated phenotypes and present our own experience of 32 MDS patients, with the aim of defining the mutation frequency of the known genes, the clinical spectrum of the diseases, and the genotype–phenotype correlations. Five of our patients carried previously unreported mutations in one of the eight MDS genes.
Recent findings regarding differences in tinnitus-related neural activity according to onset age have raised a question on possible onset age-related differences in neural substrates of distress. Hence we collected quantitative... more
Recent findings regarding differences in tinnitus-related neural activity according to onset age have raised a question on possible onset age-related differences in neural substrates of distress. Hence we collected quantitative electroencephalography (qEEG) findings of 28 late-onset tinnitus (LOT) and 29 early-onset tinnitus (EOT) (mean onset age 52.3 and 29.0 years, respectively) participants. According to the tinnitus questionnaire (TQ) score grade, LOTs were then subdivided into 13 high distress (HD; TQ grade 3 or 4) and 15 low distress (LD; TQ grade 1 or 2), while EOTs into 14 HD and 15 LD. Compared to the EOT group, the LOT group demonstrated increased qEEG source-localized activity and functional connectivity primarily in the anterior cingulate cortex (ACC) and parahippocampus. In subgroup comparisons, the ACC was activated more in HD-LOT participants than in LD-LOT participants for the beta 1, beta 2 and gamma frequency bands, while the left orbitofrontal cortex and left dors...
Prevalence findings for the elderly are artificially low, most likely due to insufficient consideration of age-related cognitive abilities in diagnostic interviews.Aims: (1) To describe the rationale for the development of an age-adapted... more
Prevalence findings for the elderly are artificially low, most likely due to insufficient consideration of age-related cognitive abilities in diagnostic interviews.Aims: (1) To describe the rationale for the development of an age-adapted Composite International Diagnostic Interview (CIDI65+) for use in a European project (MentDis_ICF65+). (2) To examine its test–retest reliability.Methods: Based on substantive pilot work the CIDI standard questions were shortened, broken down into shorter subsets and combined with sensitization questions and dimensional measures. Test–retest was determined in N = 68 subjects aged 60–79 years via two independent examinations by clinical interviewers using kappa (sensitivity, specificity) for categorical and intraclass correlation (ICC) coefficients for dimensional measures.Results: Test–retest reliability was good for any mental disorder (κ = 0.63), major depression (κ = 0.55), anxiety (κ = 0.62, range = 0.30–0.78), substance (κ = 0.77, range = 0.71–...
Mutations in the DJ-1 gene have recently been shown to cause autosomal recessive Parkinson's disease. To estimate the prevalence of this mutation, an analysis was undertaken of 39 index cases of Parkinson's disease in whom a... more
Mutations in the DJ-1 gene have recently been shown to cause autosomal recessive Parkinson's disease. To estimate the prevalence of this mutation, an analysis was undertaken of 39 index cases of Parkinson's disease in whom a family history suggested autosomal recessive inheritance. No DJ-1 mutations were found in these patients, indicating that this gene is unlikely to be of numerical significance in clinical practice. The hypothesis was also tested that young onset Parkinson's disease patients in whom, despite extensive analysis, only a single heterozygous parkin mutation was found, might harbour a second mutation in the DJ-1 gene--that is, digenic inheritance. No patient was found with a single mutation in both DJ-1 and parkin genes, making this mode of inheritance unlikely. Finally it was confirmed that PARK6 and PARK7 (DJ-1), despite being phenotypically similar and mapping to the same small chromosomal region of 1p36, are caused by mutations in separate genes.
Mutations in the beta-amyloid precursor protein gene (APP) have been found in familial early-onset Alzheímer’s disease (AD). DNA variants at several genes have been linked to the risk of developing the most common late-onset form of AD... more
Mutations in the beta-amyloid precursor protein gene (APP) have been found in familial early-onset Alzheímer’s disease (AD). DNA variants at several genes have been linked to the risk of developing the most common late-onset form of AD (LOAD). A few studies analyzed the contribution of APP variants to LOAD, with negative or conflicting results. We determined the variation in the 18 APP exons and flanking intronic sequences in a total of 350 LOAD patients from Spain. A total of 13 nucleotide changes were found and 6 were new and not found among 340 healthy controls, including the only missense change (D243N). The in silico analysis suggested that none of them would have an effect on pre-mRNA splicing or protein folding (D243N). Patients and controls were also genotyped for three APP promoter polymorphisms, and none of them was significantly associated with LOAD. We concluded that APP variants would not contribute to the risk of developing LOAD in our population.
Background The recessive ataxias are a heterogeneous group of neurodegenerative disorders characterized by cerebellar ataxia associated with a number of different neurologic, ophthalmologic, or general signs. They are often difficult to... more
Background The recessive ataxias are a heterogeneous group of neurodegenerative disorders characterized by cerebellar ataxia associated with a number of different neurologic, ophthalmologic, or general signs. They are often difficult to classify in clinical ...
The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report... more
The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the French language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations and construct validity (convergent and discriminant validity). A to...
We addressed the following three questions: (i) are there sex differences in outcome in the functional psychoses?, (ii) what is their effect size, and which variables mediate the effect of sex on outcome?, (iii) is the effect of sex... more
We addressed the following three questions: (i) are there sex differences in outcome in the functional psychoses?, (ii) what is their effect size, and which variables mediate the effect of sex on outcome?, (iii) is the effect of sex diagnosis-specific? In a prospective study of 166 patients with recent onset psychosis, we established that 4-year outcome was more favourable for women. Female patients more often had a remitting illness course (OR = 3.0; 95% CI: 1.5-5.9), were living independently 14% (4-24%) more of the time, had less evidence of negative symptoms over the follow-up period (OR = 0.3; 0.2-0.7) and were more likely to be employed at follow-up (3.6; 1.8-7.6). The findings did not appear diagnosis-specific, although the sample size was small to test for interaction with diagnostic category. Baseline occupational and social adjustment, clinical expression of illness and age and type of onset explained up to 60% of the sex effect. The processes underlying these factors mediate the effect of sex on outcome.
Mutations in several genes such as parkin can be detected in up to 20% of patients with early-onset Parkinson's disease (EOPD). The aim of our study was to determine the frequency of parkin alterations and phenotypic characteristics... more
Mutations in several genes such as parkin can be detected in up to 20% of patients with early-onset Parkinson's disease (EOPD). The aim of our study was to determine the frequency of parkin alterations and phenotypic characteristics in Czech EOPD patients. A total of 45 EOPD individuals (age at onset <45 years) were phenotyped and screened for parkin mutations. In total, 19 patients (42.2%) were carriers of previously described heterozygous genetic alterations. Parkin mutations (Ex2del, R402C) were identified in two (4.4%) cases, non-pathogenic variant A82E plus polymorphism D394N occurred in one (2.2%) patient and parkin polymorphisms (3x S167N, 1x R334C, 7x V380L, 4x D394N) were found in 15 (34.9%) individuals. Furthermore, the G2019S mutation in the LRRK2 gene was found in one (2.2%) subject. The clinical characteristics of our patients correspond to previous descriptions of EOPD phenotype. This is the first report on EOPD-associated genetic alterations among Czech patient...
Early onset dementia (EOD) poses specific challenges and issues for both the patient and (in)formal care. This study explores the use of (in)formal care prior to institutionalization, and its association with patient and caregiver... more
Early onset dementia (EOD) poses specific challenges and issues for both the patient and (in)formal care. This study explores the use of (in)formal care prior to institutionalization, and its association with patient and caregiver characteristics. Participants were part of a community-based prospective longitudinal study of 215 patients and their informal caregivers. Baseline data of a subsample of 215 patient-caregiver dyads were analyzed. Analyses of covariance were performed to determine correlates of (in)formal care use assessed with the Resource Utilization in Dementia (RUD)-Lite questionnaire. Informal care had a 3:1 ratio with formal care. Supervision/surveillance constituted the largest part of informal care. In more than half of cases, patients had only one informal caregiver. The amount of informal care was associated with disease severity, showing more informal care hours in advanced disease stages. Fewer informal care hours were related to more caregiver working hours, e...