Subject(s)
Heroin Dependence/complications , Radiculopathy/etiology , Acute Disease , Adult , Humans , MaleABSTRACT
A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) can cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). We assessed its frequency in 781 sporadic ALS (sALS) and 155 familial ALS (fALS) cases, and in 248 Spanish controls. We tested the presence of the reported founder haplotype among mutation carriers and in 171 Ceph Europeans from Utah (CEU), 170 Yoruba Africans, 81 Han Chinese, and 85 Japanese subjects. The C9orf72 expansion was present in 27.1% of fALS and 3.2% of sALS. Mutation carriers showed lower age at onset (P = 0.04), shorter survival (P = 0.02), greater co-occurrence of FTD (P = 8.2 × 10(-5)), and more family history of ALS (P = 1.4 × 10(-20)), than noncarriers. No association between alleles within the normal range and the risk of ALS was found (P = 0.12). All 61 of the mutation carriers were tested and a patient carrying 28 hexanucleotide repeats presented with the founder haplotype. This haplotype was found in 5.6% Yoruba Africans, 8.9% CEU, 3.9% Japanese, and 1.6% Han Chinese chromosomes.
Subject(s)
Amyotrophic Lateral Sclerosis/genetics , DNA Repeat Expansion/genetics , Genetic Predisposition to Disease/genetics , Proteins/genetics , Africa/ethnology , Aged , Aged, 80 and over , Amyotrophic Lateral Sclerosis/ethnology , Asian People/genetics , C9orf72 Protein , China/ethnology , DNA Mutational Analysis , Ethnicity/genetics , Europe/ethnology , Female , Gene Frequency , Genetic Predisposition to Disease/ethnology , Haplotypes , Heterozygote , Humans , Japan/ethnology , Kaplan-Meier Estimate , Male , Mutation , Polymorphism, Single Nucleotide , SpainABSTRACT
Myofibrillar myopathies (MFM) are a group of disorders associated with mutations in DES, CRYAB, MYOT, ZASP, FLNC, or BAG3 genes and characterized by disintegration of myofibrils and accumulation of degradation products into intracellular inclusions. We retrospectively evaluated 53 MFM patients from 35 Spanish families. Studies included neurologic exam, muscle imaging, light and electron microscopic analysis of muscle biopsy, respiratory function testing and cardiologic work-up. Search for pathogenic mutations was accomplished by sequencing of coding regions of the six genes known to cause MFM. Mutations in MYOT were the predominant cause of MFM in Spain affecting 18 of 35 families, followed by DES in 11 and ZASP in 3; in 3 families the cause of MFM remains undetermined. Comparative analysis of DES, MYOT and ZASP associated phenotypes demonstrates substantial phenotypic distinctions that should be considered in studies of disease pathogenesis, for optimization of subtype-specific treatments and management, and directing molecular analysis.
Subject(s)
Muscular Diseases/classification , Muscular Diseases/pathology , Myofibrils/pathology , Phenotype , Adaptor Proteins, Signal Transducing/genetics , Adolescent , Adult , Age of Onset , Aged , Biopsy , Connectin , Cytoskeletal Proteins/genetics , Desmin/genetics , Female , Humans , LIM Domain Proteins/genetics , Magnetic Resonance Imaging , Male , Microfilament Proteins , Middle Aged , Muscle Proteins/genetics , Muscular Diseases/genetics , Mutation/genetics , Retrospective Studies , Spain , Young AdultABSTRACT
OBJETIVOS: Estudiar la disfunción vesicoesfinteriana en 108 pacientes diagnosticados de esclerosis múltiple (EM). MÉTODOS: Se revisan 108 historias clínicas de pacientes diagnosticados de esclerosis múltiple, analizando los que presentaban sintomatología miccional. A estos pacientes se les practicaba un estudio urodinámico completo y las pruebas complementarias necesarias según su sintomatología. Para la clasificación clínica de la EM se utilizó la clasificación de Blaivas. RESULTADOS: 64 de los 108 pacientes presentaban clínica miccional atribuible a la EM (59,2 por ciento), en el 75 por ciento la clínica era a brotes y en el 25 por ciento era progresiva. En un 6 por ciento de los pacientes esta clínica miccional fue la primera sintomatología de la EM. En el estudio urodinámico, un 73 por ciento de los pacientes presentaba hiperreflexia del detrusor, un 14 por ciento hiporreflexia y un 13 por ciento un estudio urodinámico normal. Las complicaciones fueron siempre de tipo infeccioso y ningún paciente presentó complicaciones en el tracto urinario superior. CONCLUSIONES: La disfunción vesicoesfinteriana en la EM es frecuente, la mayoría de los paciente presentan hiperreflexia vesical. Las complicaciones urológicas suelen ser infecciosas y es rara la afectación del tracto urinario superior (AU)
