Spinal muscular atrophy among the Roma (Gypsies) in Bulgaria and Hungary

Spinal muscular atrophy is one of the most common autosomal recessive disorders, classified into three major clinical forms. It is caused mainly by deletions or gene conversions of the telomeric survival motor neuron gene (SMN1) on human chromosome 5. We have conducted molecular studies of the disorder in genetically isolated Romani (Gypsy) communities in Bulgaria and Hungary, where spinal muscular atrophy appears to have different prevalence and both mild and severe spinal muscular atrophy phenotypes have been diagnosed. We have observed three distinct genetic defects which, in different combinations, lead to different forms of the disease. The similar chromosomal background on which the different mutations occur suggests a common origin and founder effect, with rearrangements of a single ancestral chromosome resulting in a diversity of molecular defects.     

Longitudinal variations of characteristic frequencies of skeletal muscle fibre potentials detected by a bipolar electrode or multi-electrode

We aimed to reveal reasons for longitudinal variations of characteristic frequencies of electromyographic signals detected by surface longitudinal multi-electrodes. Since the terminal phases were reduced in bipolar recordings, wetested whether the frequency variations reflected the effects of the excitation origin and extinction as in monopolar recordings. A precise and fast convolution method to calculate the signals detected by a multielectrode was suggested. The contribution of different electrode poles was introduced in the impulse response. When a longitudinal multi-electrode with an even number of poles was positioned above the end-plate of asymmetrical fibres, the signal mainly reflected the processes of the excitation extinction. This increased the signal mean and median frequencies. Although the effects of origin and extinction of the excitation were significantly reduced in the spatially filtered signals, the frequency variations along the fibre reflected these intrinsic features of any skeletal muscle fibre of finite length.     

Congenital cataracts facial dysmorphism neuropathy syndrome, a novel complex genetic disease in Balkan Gypsies: clinical and electrophysiological observations.

During a study of hereditary motor and sensory neuropathy-Lom in Bulgaria, a previously unrecognized neurological disorder was encountered, mainly in Wallachian Gypsies, who represent a relatively recent genetic isolate. The disorder has been termed the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome to emphasize its salient features. Fifty individuals from 19 extended pedigrees were identified and examined clinically and electrophysiologically. At least 1 patient from each family was admitted to the hospital in Sofia for full investigation. Pedigree analysis indicates autosomal recessive inheritance. The disorder is recognized in infancy by the presence of congenital cataracts and microcorneas. A predominantly motor neuropathy beginning in the lower limbs and later affecting the upper limbs develops during childhood and leads to severe disability by the third decade. Associated neurological features are a moderate nonprogressive cognitive deficit in most affected individuals together with pyramidal signs and mild chorea in some. Accompanying nonneurological features include short stature, characteristic facial dysmorphism, and hypogonadotrophic hypogonadism. Nerve conduction studies suggest a hypomyelinating/demyelinating neuropathy, confirmed by nerve biopsy. The CCFDN syndrome is thus a pleomorphic autosomal recessive disorder displaying a combination of neurological and nonneurological features.     

Human cytomegalovirus DNA detection in a recurrent glioblastoma multiforme tumour,but not in whole blood: a case report and discussion about the HCMV latency and therapy perspectives

Journal of NeuroVirology - In the current study, a 58-year-old male patient presented with recurrent glioblastoma multiforme (GBM). The patient underwent surgical resection, 4 months...     

A family study of complex chromosome rearrangement involving chromosomes 1, 8, and 11 and its reproductive consequences

Complex chromosome translocations are structural chromosomal rearrangements involving three or more chromosomes and more than two breakpoints. A complex chromosome rearrangement was detected in a phenotypically normal female patient that was referred to the hospital for genetic counseling due to reproductive failure. A cytogenetic evaluation was performed, according to standard method of chromosomal analysis, using G-banding technique. The patient’s karyotype showed a balanced complex chromosome rearrangement (BCCR) involving chromosomes 1, 8, and 11 with three breakpoints 1p31, 8q13, and 11q23. The karyotype designed according to ISCN (2013), is 46,XX,t(1;8;11)(p31;q13;q23) (8qter→8q13::1p31→1qter;8pter→8q13::11q23→11qter;11pter→11q23::1p31→1pter). Additionally, the proband’s mother and brother were tested, resulting in the same exact translocation. In this study, we describe all possible meiotic segregations regarding this translocation, as well as the clinical phenotypes which could arise, if unbalanced products of conception survive. This is a rare case of familial complex chromosome rearrangement, giving a view for its reproductive consequences.     

Lifetime exposure to self-reported occupational noise and prevalent rheumatoid arthritis in the National Health and Nutrition Examination Survey (2011–2012)

Multiple risk factors for rheumatoid arthritis (RA) have been studied, but there is a dearth of research on occupational noise, which is highly prevalent in the United States (U.S.). This study aimed to determine whether occupational noise exposure was associated with an elevated risk of prevalent RA in the U.S. general population. Data from the 2011 to 2012 cross-sectional, population-based National Health and Nutrition Examination Survey were used for secondary analysis. Self-reported lifetime exposure to very loud noise was linked to self-reported doctor-diagnosed RA in a sample of 4192 participants. Weighted logistic regression was used to obtain nationally representative prevalence odds ratios (OR). The main and fully adjusted models yielded OR = 3.98 (95% CI: 1.74, 9.11) and OR = 2.84 (95% CI: 1.23, 6.57) for participants exposed for ≥ 15 years compared to never exposed participants. Excluding those diagnosed with RA more than five years before the interview, the effect dropped to OR = 3.67 (95% CI: 1.06, 12.75) in the main model, and was no longer significant in the fully adjusted model (OR = 2.68, 95% CI: 0.80, 8.96). The only significant effect modifier was race/ethnicity, with higher risk in Non-Hispanic whites. To conclude, long-term occupational noise exposure might be a modifiable risk factor for RA, but currently, the evidence base is very thin and tenuous.     

Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease.

Intermittent stimulation of striatal dopaminergic receptors seems to contribute to motor dysfunction in advanced Parkinson's disease (PD). With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5-HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5-HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3-week, double-blind, placebo-controlled, proof-of-concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa-induced dyskinesias and prolonged its antiparkinsonian response (P < or = 0.05). Under the conditions of this study, our findings suggest that 5-HT1A receptor stimulation in levodopa-treated parkinsonian patients can modulate striatal dopaminergic function and that 5-HT1A agonists may be useful as levodopa adjuvants in the treatment of PD.