Dominant or recessive mutations in the RYR1 gene causing central core myopathy in Brazilian patients

Central Core Disease (CCD) is an inherited neuromuscular disorder characterized by the presence of cores in muscle biopsy. CCD is caused by mutations in the RYR1 gene. This gene encodes the ryanodine receptor 1, which is an intracellular calcium release channel from the sarcoplasmic reticulum to the cytosol in response to depolarization of the plasma membrane. Mutations in this gene are also associated with susceptibility to Malignant Hyperthermia (MHS).In this study, we evaluated 20 families with clinical and histological characteristics of CCD to identify primary mutations in patients, for diagnosis and genetic counseling of the families.We identified variants in the RYR1 gene in 19/20 families. The molecular pathogenicity was confirmed in 16 of them. Most of these variants (22/23) are missense and unique in the families. Two variants were recurrent in two different families. We identified six families with biallelic mutations, five compound heterozygotes with no consanguinity, and one homozygous, with consanguineous parents, resulting in 30% of cases with possible autosomal recessive inheritance. We identified seven novel variants, four of them classified as pathogenic. In one family, we identified two mutations in exon 102, segregating in cis, suggesting an additive effect of two mutations in the same allele.This work highlights the importance of using Next-Generation Sequencing technology for the molecular diagnosis of genetic diseases when a very large gene is involved, associated to a broad distribution of the mutations along it. These data also influence the prevention through adequate genetic counseling for the families and cautions against malignant hyperthermia susceptibility.Key words: central core disease, RYR1, Next Generation Sequencing     

AIDS in adults 50 years of age and over: characteristics,trends and spatial distribution of the risk

Objective

to analyze the sociodemographic characteristics, epidemic trend and spatial distribution of the risk of AIDS in adults 50 years of age and over.

Method

population-based, ecological study, that used secondary data from the Notifiable Disease Information System (Sinan/AIDS) of Paraíba state from the period January 2000 to December 2010.

Results

during the study period, 307 cases of AIDS were reported among people 50 years of age or over. There was a predominance of males (205/66, 8%), mixed race, and low education levels. The municipalities with populations above 100 thousand inhabitants reported 58.5% of the cases. There was a progressive increase in cases among women; an increasing trend in the incidence (positive linear correlation); and an advance in the geographical spread of the disease, with expansion to the coastal region and to the interior of the state, reaching municipalities with populations below 30 thousand inhabitants. In some locations the risk of disease was 100 times greater than the relative risk for the state.

Conclusion

aging, with the feminization and interiorization of the epidemic in adults 50 years of age and over, confirms the need for the induction of affirmative policies targeted toward this age group.     

Histopathology and immunohistochemistry of tissues outside central nervous system in bovine rabies

We performed a histopathological and immunohistochemical study of tissues outside the central nervous system in 48 cases of bovine rabies confirmed by direct immunofluorescence and/or immunohistochemistry (IHC) of the central nervous system. In the bovines of this study, mononuclear inflammation in all ganglia (trigeminal, spinal, stellate, and celiac) and adrenal medulla was observed. This injury also occurred in 85 % of neuro-pituitaries in 55 % of pars intermediate and 15 % of the pars distalis of pituitary evaluated. IHC was positive in 92.31 % of lumbar spinal ganglia, 90.9 % of trigeminal ganglia, stellate ganglia of 41.67 and 16.67 % of the celiac ganglia. One of the evaluated adrenal (1/17) showed strong immunohistochemical labeling in the cytoplasm of pheochromocytes. The pituitary IHC was positive in one case in the neurohypophysis (1/20) and in one case in the pars intermedia of the adenohypophysis (1/20). Data from this study indicate that in suspected cases of rabies, besides the complex pituitary rete mirabile and trigeminal ganglion, the evaluation of other ganglia, particularly the lumbar spinal, and adrenal may also contribute to the diagnosis and understanding of the clinical presentation and pathogenesis of the disease in bovines.     

Growth of children with end-stage renal disease undergoing daily hemodialysis

Background

The aim of this report is to describe the effect of daily hemodialysis on the growth of children with end-stage renal disease (ESRD).

Methods

We performed a prospective, observational study on 24 children with ESRD undergoing daily hemodialysis (DHD). The control group comprised 26 children on concurrent conventional hemodialysis (CHD), and the follow-up for both groups was 9.3?±?3.0 months. No patient received growth hormone (GH) therapy.

Results

At the onset of the study, the height-for-age Z-score was ?2.12?±?1.54 in the CHD group and ?2.84?±?2.27 in the DHD group (p?=?0.313). Assuming an increase of 0.5 standard deviation scores (SDS) of the height-for-age parameter as an improvement of growth, there were 33 % of patients in the DHD group and 8 % in the CHD group (p?=?0.035). The cumulative probability of gain in height for age at 12 months was 40 % in the DHD group versus 15 % in the CHD group (p?=?0.047). Also, 98 % of patients in the DHD group had an adequate total caloric intake, whereas 38 % in the CHD group reached this goal (p?<?0.001). No patient left the study due to intensification of the dialysis modality.

Conclusions

Our data show that the DHD favored a 0.5 SDS height gain in a third of patients without GH treatment. Dialysis intensification was not a cause for treatment dropouts, and DHD should be considered as a treatment for selected cases, especially small children.     

Multidrug-Resistant Nontuberculous Mycobacteria Isolated from Cystic Fibrosis Patients

Worldwide, nontuberculous mycobacteria (NTM) have become emergent pathogens of pulmonary infections in cystic fibrosis (CF) patients, with an estimated prevalence ranging from 5 to 20%. This work investigated the presence of NTM in sputum samples of 129 CF patients (2 to 18 years old) submitted to longitudinal clinical supervision at a regional reference center in Rio de Janeiro, Brazil. From June 2009 to March 2012, 36 NTM isolates recovered from 10 (7.75%) out of 129 children were obtained. Molecular identification of NTM was performed by using PCR restriction analysis targeting the hsp65 gene (PRA-hsp65) and sequencing of the rpoB gene, and susceptibility tests were performed that followed Clinical and Laboratory Standards Institute recommendations. For evaluating the genotypic diversity, pulsed-field gel electrophoresis (PFGE) and/or enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) was performed. The species identified were Mycobacterium abscessus subsp. bolletii (n = 24), M. abscessus subsp. abscessus (n = 6), Mycobacterium fortuitum (n = 3), Mycobacterium marseillense (n = 2), and Mycobacterium timonense (n = 1). Most of the isolates presented resistance to five or more of the antimicrobials tested. Typing profiles were mainly patient specific. The PFGE profiles indicated the presence of two clonal groups for M. abscessus subsp. abscessus and five clonal groups for M. abscesssus subsp. bolletii, with just one clone detected in two patients. Given the observed multidrug resistance patterns and the possibility of transmission between patients, we suggest the implementation of continuous and routine investigation of NTM infection or colonization in CF patients, including countries with a high burden of tuberculosis disease.     

Evaluation of light-touch sensation in the buccal mucosa of leprosy patients

Objective

The aim of this study is to evaluate the light-touch sensation of the oral mucosa in leprosy patients.

Materials and methods

A cross-sectional study included 228 adults, 133 being leprosy patients and 95 normal controls. To assess light-touch sensation, the five-filament standard Semmes–Weinstein kit in eight regions of the oral mucosa was used. Chi-square test was used to verify the differences in responses between the studied groups.

Results

Normal sensation was predominant in both groups, and diminished sensation was found also in the nonleprosy group. Normal controls showed diminished light-touch sensation in at least one point, which may be attributed to the definition of sensation normality. The chi-square test revealed no significant difference between the two groups (p?=?0.43171). Severe diminished sensation was detected only in the leprosy group.

Conclusion

It is concluded that altered light-touch sensation in the oral cavity may not be a common feature in leprosy.

Clinical relevance

Decreased or lost sensation in skin lesions is a paramount in leprosy diagnosis; however, clinicians must be aware that this seems not to be true in the oral mucosa in leprosy cases for diagnosis purpose.