ABSTRACT
BACKGROUND: In hereditary myopathy with early respiratory failure (HMERF), cytoplasmic bodies (CBs) are often localised in subsarcolemmal regions, with necklace-like alignment (necklace CBs), in muscle fibres although their sensitivity and specificity are unknown. OBJECTIVE: To elucidate the diagnostic value of the necklace CBs in the pathological diagnosis of HMERF among myofibrillar myopathies (MFMs). METHODS: We sequenced the exon 343 of TTN gene (based on ENST00000589042), which encodes the fibronectin-3 (FN3) 119 domain of the A-band and is a mutational hot spot for HMERF, in genomic DNA from 187 patients from 175 unrelated families who were pathologically diagnosed as MFM. We assessed the sensitivity and specificity of the necklace CBs for HMERF by re-evaluating the muscle pathology of our patients with MFM. RESULTS: TTN mutations were identified in 17 patients from 14 families, whose phenotypes were consistent with HMERF. Among them, 14 patients had necklace CBs. In contrast, none of other patients with MFM had necklace CBs except for one patient with reducing body myopathy. The sensitivity and specificity were 82% and 99%, respectively. Positive predictive value was 93% in the MFM cohort. CONCLUSIONS: The necklace CB is a useful diagnostic marker for HMERF. When muscle pathology shows necklace CBs, sequencing the FN3 119 domain of A-band in TTN should be considered.
Subject(s)
Cytoplasm/pathology , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/metabolism , Muscle Proteins/metabolism , Muscular Diseases/diagnosis , Muscular Diseases/metabolism , Protein Aggregation, Pathological/metabolism , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/metabolism , Adult , Aged , Biomarkers/metabolism , Connectin/genetics , Cytoplasm/ultrastructure , Female , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/pathology , Humans , Male , Middle Aged , Muscle Proteins/genetics , Muscle, Skeletal/pathology , Muscle, Skeletal/ultrastructure , Muscular Diseases/genetics , Muscular Diseases/pathology , Mutation , Respiratory Insufficiency/genetics , Respiratory Insufficiency/pathology , Sensitivity and SpecificityABSTRACT
BACKGROUND: Aspiration pneumonia (AP) following cerebral infarction (CI) has been considered as one of its most serious complications. Nevertheless, there are no reports on the association between the type or location of CI and the incidence of AP. In addition, the association between dysphagia, which leads to aspiration, and the type or location of CI has never been investigated. Therefore we hypothesized that the laterality of CI affects the development of both dysphagia and AP. METHODS: We performed a retrospective cohort study to examine the association between the laterality of CI and the incidence of dysphagia and AP in 133 patients. RESULTS: AP was found in 6.0% of the group with left CI and in 0.8% of the group with right CI. A univariate logistic regression analysis revealed that left CI was a significant predictor of AP (hazard ratio, 8.81; 95% confidence interval, 1.07-72.59; p = 0.043). Left CI was a significant predictor of AP even after adjusting for age, sex, CI type, or presence of diabetes mellitus. In addition, although the frequency of dysphagia as the direct cause of AP did not differ according to laterality, the frequency of AP that ensued from dysphagia in the left CI group was greater than that observed in the right CI group. CONCLUSIONS: The group with left CI from the motor cortex to the internal capsule complicated by dysphagia exhibited a high risk of AP.
