Assuntos
Cistos Ósseos Aneurismáticos , Saco Endolinfático , Imageamento por Ressonância Magnética , Humanos , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Saco Endolinfático/diagnóstico por imagem , Saco Endolinfático/patologia , Diagnóstico Diferencial , Tomografia Computadorizada por Raios X , Neoplasias da Orelha/diagnóstico por imagem , Neoplasias da Orelha/patologia , Feminino , MasculinoRESUMO
Hearing loss is one of the most common sensory defects, affecting 5.5% of the worldwide population and significantly impacting health and social life. It is mainly attributed to genetic causes, but their relative contribution reflects the geographical region's socio-economic development. Extreme genetic heterogeneity with hundreds of deafness genes involved poses challenges for molecular diagnosis. Here we report the investigation of 542 hearing-impaired subjects from all Brazilian regions to search for genetic causes. Biallelic GJB2/GJB6 causative variants were identified in 12.9% (the lowest frequency was found in the Northern region, 7.7%), 0.4% carried GJB2 dominant variants, and 0.6% had the m.1555A > G variant (one aminoglycoside-related). In addition, other genetic screenings, employed in selected probands according to clinical presentation and presumptive inheritance patterns, identified causative variants in 2.4%. Ear malformations and auditory neuropathy were diagnosed in 10.8% and 3.5% of probands, respectively. In 3.8% of prelingual/perilingual cases, Waardenburg syndrome was clinically diagnosed, and in 71.4%, these diagnoses were confirmed with pathogenic variants revealed; seven out of them were novel, including one CNV. All these genetic screening strategies revealed causative variants in 16.2% of the cases. Based on causative variants in the molecular diagnosis and genealogy analyses, a probable genetic etiology was found in ~ 50% of the cases. The present study highlights the relevance of GJB2/GJB6 as a cause of hearing loss in all Brazilian regions and the importance of screening unselected samples for estimating frequencies. Moreover, when a comprehensive screening is not available, molecular diagnosis can be enhanced by selecting probands for specific screenings.
Assuntos
Perda Auditiva , Brasil/epidemiologia , Estudos de Coortes , Conexina 26/genética , Conexinas/genética , Testes Genéticos , Perda Auditiva/diagnóstico , Perda Auditiva/genética , Humanos , MutaçãoRESUMO
OBJECTIVES: Collagen VI-related dystrophies (COL6-RDs) have a broad clinical spectrum and are caused by mutations in the COL6A1, COL6A2 and COL6A3 genes. Despite the clinical variability, two phenotypes are classically recognized: Bethlem myopathy (BM, milder form) and Ullrich congenital muscular dystrophy (UCMD, more severe form), with many patients presenting an intermediate phenotype. In this work, we present clinical and genetic data from 28 patients (27 families), aged 6-38 years (mean of 16.96 years), with COL6-RDs. PATIENTS AND METHODS: Clinical, muscle histology and genetic data are presented. COL6A1, COL6A2 and COL6A3 genes were analyzed by next-generation sequencing (NGS). RESULTS: Homozygous or heterozygous variants were found in COL6A1 (12 families), COL6A2 (12 families) and COL6A3 (3 families). Patients with the severe UCMD phenotype (three cases) had a homogeneous clinical picture characterized by neonatal onset of manifestations, no gait acquisition and a stable course, but with severe respiratory involvement. Most of the patients with the mild UCMD phenotype had neonatal onset of manifestations (88.8 %), delayed motor development (66.6 %), slowly progressive course, pulmonary involvement (55.5 %) and loss of the walking capacity before the age of 10 (66.6 %). In the intermediate group (nine patients), some children had neonatal onset of manifestations (44.5 %) and delayed motor development (88.9 %); but all of them achieved the ability to walk and were still ambulatory. Some patients that had the BM phenotype presented neonatal manifestations (57.1 %); however, all of them had normal motor development and normal pulmonary function. Only one patient from the group of BM lost the walking capacity during the evolution of the disease. Other frequent findings observed in all groups were joint retractions, spinal deformities, distal hyperextensibility, congenital hip dislocation and keloid formation. CONCLUSION: COL6-RDs present variable clinical manifestations, but common findings are helpful for the clinical suspicion. NGS is a valuable approach for diagnosis, providing useful information for the genetic counseling of families.
Assuntos
Colágeno Tipo VI/genética , Contratura/fisiopatologia , Distrofias Musculares/congênito , Esclerose/fisiopatologia , Adolescente , Adulto , Idade de Início , Brasil , Criança , Estudos de Coortes , Contratura/genética , Contratura/patologia , Progressão da Doença , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Luxação Congênita de Quadril/fisiopatologia , Humanos , Queloide/fisiopatologia , Masculino , Músculo Esquelético/patologia , Distrofias Musculares/genética , Distrofias Musculares/patologia , Distrofias Musculares/fisiopatologia , Esclerose/genética , Esclerose/patologia , Curvaturas da Coluna Vertebral/fisiopatologia , Adulto JovemRESUMO
The most common causes of congenital myasthenic syndromes (CMS) are CHRNE mutations, and some pathogenic allelic variants in this gene are especially frequent in certain ethnic groups. In the southern region of Brazil, a study found the c.130dupG CHRNE mutation in up to 33% of families with CMS. Here, we aimed to verify the frequency of this mutation among individuals with CMS in a larger cohort of CMS patients from different areas of Brazil and to characterize clinical features of these patients. Eighty-four patients with CMS, from 72 families, were clinically evaluated and submitted to direct sequencing of the exon 2 of CHRNE. The c.130dupG mutation was found in 32 patients (23 families), with 26 patients (19 families, 26.3%) in homozygosis, confirming its high prevalence in different regions of Brazil. Among the homozygous patients, the following characteristics were frequent: onset of symptoms before 2 years of age (92.3%), little functional restriction (92.3%), fluctuating symptoms (100%), ocular muscle impairment (96.1%), ptosis (100%), limb weakness (88.4%), response to pyridostigmine (100%), facial involvement (77%), and bulbar symptoms (70.8%). The pretest probability of finding at least one allele harbouring the c.130dupG mutation was 38.1%. Selecting only patients with impaired eye movement together with limb weakness and improvement with pyridostigmine, the probability increases to 72.2%. This clinical pre-selection of patients is likely a useful tool for regions where CHRNE mutations have a founder effect. In conclusion, the CHRNE mutation c.130dupG leads to fairly benign natural course of the disease with relative homogeneity.
Assuntos
Mutação , Síndromes Miastênicas Congênitas/genética , Receptores Nicotínicos/genética , Adolescente , Adulto , Idade de Início , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Éxons , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Miastênicas Congênitas/tratamento farmacológico , Síndromes Miastênicas Congênitas/epidemiologia , Síndromes Miastênicas Congênitas/patologia , Fenótipo , Prevalência , Adulto JovemRESUMO
We investigated 313 unrelated subjects who presented with hearing loss to identify the novel genetic causes of this condition in Brazil. Causative GJB2/GJB6 mutations were found in 12.7% of the patients. Among the familial cases (100/313), four were selected for exome sequencing. In one case, two novel heterozygous variants were found and were predicted to be pathogenic based on bioinformatics tools, that is, p.Ser906* (MYO6) and p.Arg42Cys (GJB3). We confirmed that this nonsense MYO6 mutation segregated with deafness in this family. Only the proband and her unaffected mother exhibited the GJB3 mutation, which is in the same amino acid of a known Erythrokeratodermia variabilis mutation. None of the patients exhibited this skin disease, but the proband exhibited a more severe hearing loss. Hence, the GJB3 mutation was considered to be a variant of uncertain significance. In conclusion, we described a novel nonsense MYO6 mutation that was responsible for the hearing loss in a Brazilian family. This mutation resides in the neck domain of myosin-VI after the motor domain. Thus, our data give further support for genotype-phenotype correlations, which state that when the motor domain of the protein is functioning, the hearing loss is milder and has a later onset. The three remaining families without mutations in the known genes suggest that there are still deafness genes to be revealed.
Assuntos
Códon sem Sentido , Surdez/genética , Exoma , Cadeias Pesadas de Miosina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Conexina 26 , Conexina 30/genética , Conexinas/genética , Feminino , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Análise de Sequência de DNA , Adulto JovemRESUMO
BACKGROUND: Nemaline myopathy is a rare congenital disease of skeletal muscle characterized by muscle weakness and hypotonia, as well as the diagnostic presence of nemaline rods in skeletal muscle fibers. Nemaline myopathy is genetically and phenotypically heterogeneous and, so far, mutations in 11 different genes have been associated with this disease. Dominant mutations in ACTA1 are the second most frequent genetic cause of nemaline myopathy and can lead to a variety of clinical and histologic phenotypes. PATIENTS AND METHODS: We present a series of ACTA1-related cases from a Brazilian cohort of 23 patients with nemaline myopathy, diagnosed after Sanger sequencing the entire coding region of ACTA1, and review the literature on ACTA1-related nemaline myopathy. RESULTS: The study confirmed ACTA1 mutations in four patients, including one with intranuclear rods, one with large intracytoplasmic aggregates, and two with nemaline intracytoplasmic rods. A repeat muscle biopsy in one patient did not show histological progression. CONCLUSION: Despite the recognized phenotypic variability in ACTA1-related nemaline myopathy, clinical and histological presentations appear to correlate with the position of the mutation, which confirms emerging genotype/phenotype correlations and better predict the prognosis of affected patients.
Assuntos
Actinas/genética , Músculo Esquelético/patologia , Mutação/genética , Miopatias da Nemalina/genética , Adolescente , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: VCP (valosin-containing protein gene) variants have been associated with peripheral and central neurodegenerative processes, including inclusion body myopathy (IBM), Paget disease of bone (PDB), frontotemporal dementia (FTD), and familial amyotrophic lateral sclerosis (ALS) type 14. The combination of IBM, PDB (IBMPFD1) can presented in one individual. However, the association of IBMPFD1 and ALS in the same family is rare. METHODS: We reported three individuals from a Brazilian kindred with intrafamilial phenotype variability. Whole exome sequencing (WES) of the proband was performed and revealed a novel VCP variant. VCP Sanger sequencing was performed in the proband and his family members to confirm WES finding and segregation. We performed a systematic review of the literature regarding the genotypic-phenotypic VCP correlations. RESULTS: Each individual presented with either myopathy with rimmed vacuoles, ALS, or FTD. There was no PDB. WES of the proband identified the heterozygous variant c.271A>T (p.Asn91Tyr) in the exon 3 of VCP. Sanger sequencing confirmed the segregation of this variant in an autosomal-dominant pattern. CONCLUSION: This study expands the genotypic spectrum of the missense mutations of the VCP gene with a novel p.Asn91Tyr variant found in a Brazilian family presenting with the unusual intrafamiliar association of myopathy with rimmed vacuoles, ALS and FTD.
Assuntos
Adenosina Trifosfatases/genética , Esclerose Lateral Amiotrófica/genética , Proteínas de Ciclo Celular/genética , Saúde da Família , Demência Frontotemporal/genética , Doenças Musculares/genética , Mutação/genética , Fenótipo , Adulto , Idoso , Análise Mutacional de DNA , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteína com ValosinaRESUMO
BACKGROUND: Myotubular myopathy is a rare X-linked congenital myopathy characterized by marked neonatal hypotonia and respiratory insufficiency, facial and ocular involvement, and muscle biopsy with prominent central nuclei in the majority of muscle fibers. It is caused by mutations in MTM1, which codes for the phosphoinositides phosphatase myotubularin. In this work, we established and detailed a new cohort of six patients at the clinical, histologic, and genetic levels. PATIENTS AND METHODS: Patients were recruited after screening 3065 muscle biopsy reports from two large biopsy banks in Sao Paulo, Brazil from the years 2008 to 2013, and from referrals to a neuromuscular outpatient clinic between 2011 and 2013. We reviewed biopsy slides, evaluated patients, and Sanger sequenced MTM1 in the families. RESULTS: All patients but one had classic phenotypes with a stable course after a severe onset. Two patients died suddenly from hypovolemic shock. Muscle biopsies had been performed in five patients, all of whom showed a classic pattern with a predominance of centrally located nuclei and increased oxidative activity in the center of the fibers. Two patients showed necklace fibers, and two families had novel truncating mutations in MTM1. CONCLUSIONS: X-linked myotubular myopathy is rare in the Brazilian population. Necklace fibers might be more prevalent in this condition than previously reported. Direct Sanger sequencing of MTM1 on clinical suspicion avoids the need of a muscle biopsy.
Assuntos
Músculo Esquelético/patologia , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/patologia , Proteínas Tirosina Fosfatases não Receptoras/genética , Biópsia , Brasil , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , Face/anormalidades , Humanos , Lactente , Masculino , Miopatias Congênitas Estruturais/epidemiologia , Miopatias Congênitas Estruturais/fisiopatologia , FenótipoRESUMO
UNLABELLED: Calpainopathy is an autosomal recessive limb girdle muscular dystrophy (LGMD2A) caused by mutations in CAPN3 gene. OBJECTIVE: To present clinical and histological findings in six children with a molecular diagnosis of LGMD2A and additionally the MRI findings in two of them. METHOD: We retrospectively assessed medical records of 6 patients with mutation on CAPN3 gene. RESULTS: All patients were female (three to 12 years). The mean of age of disease onset was 9 years. All of them showed progressive weakness with predominance in lower limbs. Other findings were scapular winging, joint contractures and calf hypertrophy. One female had a more severe phenotype than her dizygotic twin sister that was confirmed by muscle MRI. Muscle biopsies showed a dystrophic pattern in all patients. CONCLUSION: In this cohort of children with LGMD2A, the clinical aspects were similar to adults with the same disorder.
Assuntos
Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Brasil , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Mutação/genética , Fenótipo , Estudos RetrospectivosRESUMO
ABSTRACT Calpainopathy is an autosomal recessive limb girdle muscular dystrophy (LGMD2A) caused by mutations in CAPN3 gene. Objective To present clinical and histological findings in six children with a molecular diagnosis of LGMD2A and additionally the MRI findings in two of them. Method We retrospectively assessed medical records of 6 patients with mutation on CAPN3 gene. Results All patients were female (three to 12 years). The mean of age of disease onset was 9 years. All of them showed progressive weakness with predominance in lower limbs. Other findings were scapular winging, joint contractures and calf hypertrophy. One female had a more severe phenotype than her dizygotic twin sister that was confirmed by muscle MRI. Muscle biopsies showed a dystrophic pattern in all patients. Conclusion In this cohort of children with LGMD2A, the clinical aspects were similar to adults with the same disorder.
RESUMO Calpainopatia é uma distrofia muscular de cinturas autossômica recessiva (LGMD2A) causada por mutações no gene CAPN3. Objetivo Apresentar os aspectos clínicos e histológicos em seis crianças com diagnostico molecular de LGMD2A e adicionalmente os achados na RNM de músculo em duas delas. Método Nos retrospectivamente analisamos os dados de prontuário de seis crianças com mutações no gene CAPN3. Resultados Todos os pacientes eram do sexo feminino (3 a 12 anos). A média de idade de inicio da doença foi de nove anos. Todos mostraram uma fraqueza progressiva com predomínio nos membros inferiores. Outros achados incluíam escapula alada, contratura de tendão de Aquiles e hipertrofia de panturrilhas. Uma menina apresentou um fenótipo mais severo quando comparado a sua irmã gêmea dizigótica o que foi confirmado pelos achados encontrados na RNM de músculo. Em todos os pacientes a biópsia muscular mostrou um padrão distrófico. Conclusão Nesta coorte de crianças com LGMD2A, os aspectos clínicos foram bastante similares a pacientes adultos com a mesma doença.
Assuntos
Criança , Pré-Escolar , Feminino , Humanos , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Brasil , Análise Mutacional de DNA , Mutação/genética , Fenótipo , Estudos RetrospectivosRESUMO
Centronuclear myopathy (CNM) is a rare congenital muscle disease characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, and can have multiple modes of inheritance in association with various genes, including MTM1, DNM2, BIN1 and RYR1. Here we analyzed 18 sporadic patients with clinical and histological diagnosis of CNM and sequenced the DNM2 gene, which codes for the dynamin 2 protein. We found DNM2 missense mutations in two patients, both in exon 8, one known (p.E368K) and one novel (p.F372C), which is found in a position of presumed pathogenicity and appeared de novo. The patients had similar phenotypes characterized by neonatal signs followed by improvement and late childhood reemergence of slowly progressive generalized muscle weakness, elongated face with ptosis and ophthalmoparesis, and histology showing fibers with radiating sarcoplasmic strands (RSS). These patients were the only ones in the series to present this histological marker, which together with previous reports in the literature suggest that, when RSS are present, direct sequencing of DNM2 mutation hot spot regions should be the first step in the molecular diagnosis of CNM, even in sporadic cases.
RESUMO
UNLABELLED: Patients with sarcoglycanopathies, which comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies, usually present with progressive weakness leading to early loss of ambulation and premature death, and no effective treatment is currently available. OBJECTIVE: To present clinical aspects and outcomes of six children with sarcoglycanopathies treated with steroids for at least one year. METHOD: Patient files were retrospectively analyzed for steroid use. RESULTS: Stabilization of muscle strength was noted in one patient, a slight improvement in two, and a slight worsening in three. In addition, variable responses of forced vital capacity and cardiac function were observed. CONCLUSIONS: No overt clinical improvement was observed in patients with sarcoglycanopathies under steroid therapy. Prospective controlled studies including a larger number of patients are necessary to determine the effects of steroids for sarcoglycanopathies.
Assuntos
Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Pregnenodionas/uso terapêutico , Sarcoglicanopatias/tratamento farmacológico , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Inherited myopathies are a heterogeneous group of disabling disorders with still barely understood pathological mechanisms. Around 40% of afflicted patients remain without a molecular diagnosis after exclusion of known genes. The advent of high-throughput sequencing has opened avenues to the discovery of new implicated genes, but a working list of prioritized candidate genes is necessary to deal with the complexity of analyzing large-scale sequencing data. Here we used an integrative data mining strategy to analyze the genetic network linked to myopathies, derive specific signatures for inherited myopathy and related disorders, and identify and rank candidate genes for these groups. Training sets of genes were selected after literature review and used in Manteia, a public web-based data mining system, to extract disease group signatures in the form of enriched descriptor terms, which include functional annotation, human and mouse phenotypes, as well as biological pathways and protein interactions. These specific signatures were then used as an input to mine and rank candidate genes, followed by filtration against skeletal muscle expression and association with known diseases. Signatures and identified candidate genes highlight both potential common pathological mechanisms and allelic disease groups. Recent discoveries of gene associations to diseases, like B3GALNT2, GMPPB and B3GNT1 to congenital muscular dystrophies, were prioritized in the ranked lists, suggesting a posteriori validation of our approach and predictions. We show an example of how the ranked lists can be used to help analyze high-throughput sequencing data to identify candidate genes, and highlight the best candidate genes matching genomic regions linked to myopathies without known causative genes. This strategy can be automatized to generate fresh candidate gene lists, which help cope with database annotation updates as new knowledge is incorporated.
Assuntos
Mineração de Dados/métodos , Estudos de Associação Genética/métodos , Doenças Musculares/genética , Ontologia Genética , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , FenótipoRESUMO
Patients with sarcoglycanopathies, which comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies, usually present with progressive weakness leading to early loss of ambulation and premature death, and no effective treatment is currently available. Objective To present clinical aspects and outcomes of six children with sarcoglycanopathies treated with steroids for at least one year. Method Patient files were retrospectively analyzed for steroid use. Results Stabilization of muscle strength was noted in one patient, a slight improvement in two, and a slight worsening in three. In addition, variable responses of forced vital capacity and cardiac function were observed. Conclusions No overt clinical improvement was observed in patients with sarcoglycanopathies under steroid therapy. Prospective controlled studies including a larger number of patients are necessary to determine the effects of steroids for sarcoglycanopathies. .
Pacientes com sarcoglicanopatias, que compreendem quatro subtipos de distrofias musculares de cinturas autossômicas recessivas, geralmente apresentam fraqueza progressiva, levando à perda precoce da deambulação e morte prematura, e não há tratamento eficaz disponível até o momento. Objetivo Descrever os aspectos clínicos e a evolução de seis crianças com sarcoglicanopatias tratados com corticosteróides por pelo menos um ano. Método Prontuários dos pacientes foram analisados retrospectivamente. Resultados Estabilização da força muscular foi observada em um paciente, uma ligeira melhora em dois, e um ligeiro agravamento em três. Além disso, foram observadas respostas variáveis de capacidade vital forçada e da função cardíaca. Conclusões Não houve melhora clínica evidente em pacientes com sarcoglicanopatias sob terapia com corticosteróides. Estudos prospectivos controlados incluindo maior número de pacientes são necessários para determinar os efeitos dos corticosteróides para sarcoglicanopatias. .
Assuntos
Criança , Feminino , Humanos , Masculino , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Pregnenodionas/uso terapêutico , Sarcoglicanopatias/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Introdução: A miopatia centronuclear é uma doença muscular congênita com apresentação clínica heterogênea, caracterizada histologicamente pela proeminência de fibras musculares com núcleos centralizados. Três formas são reconhecidas: neonatal grave, com herança ligada ao X e envolvimento do gene MTM1; autossômica dominante, com início geralmente tardio e curso mais leve, associada a mutações no gene DNM2; e autossômica recessiva, com gravidade intermediária entre as outras formas e envolvimento dos genes BIN1, RYR1 ou TTN. Apesar da identificação dos principais genes responsáveis pela doença, os métodos usuais de diagnóstico genético não encontram mutações em cerca da metade dos casos. Objetivo: O objetivo deste estudo foi a caracterização clínica, histológica e molecular de pacientes brasileiros portadores de miopatia centronuclear. Métodos: Laudos de dois bancos de biópsia muscular foram usados para identificar pacientes com diagnóstico de miopatia centronuclear nos últimos dez anos. As lâminas das biópsias foram revisadas e analisadas, e as famílias correspondentes convocadas para aplicação de protocolo clínico e coleta de sangue periférico para extração de DNA genômico. As famílias foram estudadas para os genes conhecidos por sequenciamento Sanger, MLPA, painel de genes implicados em doenças neuromusculares ou sequenciamento de exoma. Resultados: Foram convocados 24 pacientes provenientes de 21 famílias, em 16 das quais foi possível estabelecer o diagnóstico molecular. As 7 famílias com a forma neonatal grave constituíam um grupo homogêneo clínica e histologicamente, e mutações novas e conhecidas foram encontradas no gene MTM1 em 6 destas. Dois meninos deste grupo, com evolução estável, tiveram óbito súbito por choque hipovolêmico subsequente a rompimento de cisto hepático. O gene MTM1 também foi implicado em uma menina portadora manifestante, com quadro mais leve, na forma de uma macrodeleção em heterozigose, detectada por MPLA...
Introduction: Centronuclear myopathy is a heterogeneous congenital muscle disease, characterized by the prominence of centralized nuclei in muscle fibers. Three disease forms are recognized: a severe neonatal, X-linked form caused by mutations in the MTM1 gene; an autosomal dominant, late-onset milder form, associated to the DNM2 gene; and an autosomal recessive form, with intermediate severity, so far with the BIN1, RYR1 or TTN genes implicated. In spite of the identification of these genes, usual molecular diagnostic methods don't yield a molecular diagnosis in about half of cases. Objetives: The aim of this work was to study clinical, histological, and molecular aspects of centronuclear myopathy Brazilian patients. Methods: Reports taken from two muscle biopsy banks were used to identify centronuclear myopathy patients in the last ten years. Biopsy slides were reviewed and analyzed, and corresponding families recruited to apply a clinical protocol and to draw peripheral blood to extract genomic DNA. Families were studied for known genes via Sanger sequencing, MLPA, panel of genes implicated in neuromuscular diseases, or exome sequencing. Results: Twentyfour patients out of 21 families were recruited, and in 16 families molecular diagnosis was established. The 7 families with the severe neonatal form amounted to a clinically and histologically homogeneous group, and mutations, both known and novel, were found in the MTM1 gene in 6 of these. Two boys of this group, with a stable course, died suddenly of hypovolemic shock due to a hepatic cyst rupture. The MTM1 gene was also implicated in the case of a mild manifesting carrier girl with a heterozygous macrodeletion detected via MLPA...
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Biópsia , Dinamina II , Exoma , Sequenciamento de Nucleotídeos em Larga Escala , Hipotonia Muscular , Miopatias Congênitas Estruturais , Canal de Liberação de Cálcio do Receptor de RianodinaRESUMO
UNLABELLED: We ascertained whether a public health stroke unit reduces the length of hospitalization, the rate of inpatient fatality, and the mortality rate 30 days after the stroke. METHODS: We compared a cohort of stroke patients managed on a general neurology/medical ward with a similar cohort of stroke patients managed in a stroke unit. The in-patient fatality rates and 30-day mortality rates were analyzed. RESULTS: 729 patients were managed in the general ward and 344 were treated at a comprehensive stroke unit. The in-patient fatality rates were 14.7% for the general ward group and 6.9% for the stroke unit group (p<0.001). The overall mortality rate 30 days after stroke was 20.9% for general ward patients and 14.2% for stroke unit patients (p=0.005). CONCLUSIONS: We observed reduced in-patient fatalities and 30-day mortality rates in patients managed in the stroke unit. There was no impact on the length of hospitalization.
Assuntos
Isquemia Encefálica/mortalidade , Mortalidade Hospitalar , Unidades Hospitalares/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Acidente Vascular Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Brasil , Métodos Epidemiológicos , Feminino , Hospitais Públicos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de TempoRESUMO
We ascertained whether a public health stroke unit reduces the length of hospitalization, the rate of inpatient fatality, and the mortality rate 30 days after the stroke. Methods We compared a cohort of stroke patients managed on a general neurology/medical ward with a similar cohort of stroke patients managed in a str oke unit. The in-patient fatality rates and 30-day mortality rates were analyzed. Results 729 patients were managed in the general ward and 344 were treated at a comprehensive stroke unit. The in-patient fatality rates were 14.7% for the general ward group and 6.9% for the stroke unit group (p<0.001). The overall mortality rate 30 days after stroke was 20.9% for general ward patients and 14.2% for stroke unit patients (p=0.005). Conclusions We observed reduced in-patient fatalities and 30-day mortality rates in patients managed in the stroke unit. There was no impact on the length of hospitalization. .
Avaliar o impacto da unidade de AVC (acidente vascular cerebral) no sistema público de saúde sobre o tempo de internação, mortalidade hospitalar e mortalidade após 30 dias do AVC agudo. Métodos Comparamos uma coorte de pacientes com AVC agudo tratados em enfermaria neurológica ou geral (EG) com uma coorte similar de pacientes com AVC tratados em uma unidade de AVC (UAVC), em um mesmo hospital público. Resultados 729 pacientes foram conduzidos na EG e 344 foram tratados em uma UAVC. A mortalidade inicial foi de 14,7% na EG e 6,9% na UAVC (p<0,001). A mortalidade geral em 30 dias após o AVC foi de 20.9% nos pacientes tratados na EG e 14,2% naqueles tratados na UAVC (p=0,005). Conclusão Observamos significante redução da mortalidade inicial e da mortalidade após 30 dias do AVC nos pacientes tratados na UAVC. Não houve impacto sobre o tempo de internação. .