RESUMEN
Bcl2-associated athanogene 3 (BAG3) mutations have been reported to cause the myofibrillar myopathy (MFM) which shows progressive limb muscle weakness, respiratory failure, and cardiomyopathy. Myopathy patients with BAG3 mutation are very rare. We described a patient showing atypical phenotypes. We aimed to find the genetic cause of Korean patients with sensory motor polyneuropathy, myopathy and rigid spine. We performed whole exome sequencing (WES) with 423 patients with sensory motor polyneuropathy. We found BAG3 mutation in one patient with neuropathy, myopathy and rigid spine syndrome, and performed electrophysiological study, whole body MRI and muscle biopsy on the patient. A de novo heterozygous p.Pro209Leu (c.626C>T) mutation in BAG3 was identified in a female myopathy. She first noticed a gait disturbance and spinal rigidity at the age of 11, and serum creatine kinase levels were elevated ninefolds than normal. She showed an axonal sensory-motor polyneuropathy like Charcot-Marie-Tooth disease (CMT), myopathy, rigid spine and respiratory dysfunction; however, she did not show any cardiomyopathy, which is a common symptom in BAG3 mutation. Lower limb MRI and whole spine MRI showed bilateral symmetric fatty atrophy of muscles at the lower limb and paraspinal muscles. When we track traceable MRI 1 year later, the muscle damage progressed slowly. As far as our knowledge, this is the first Korean patient with BAG3 mutation. We described a BAG3 mutation patient with atypical phenotype of CMT and myopathy, and those are expected to broaden the clinical spectrum of the disease and help to diagnose it.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Enfermedad de Charcot-Marie-Tooth/genética , Miopatías Estructurales Congénitas/genética , Adolescente , Adulto , Enfermedad de Charcot-Marie-Tooth/sangre , Enfermedad de Charcot-Marie-Tooth/diagnóstico por imagen , Enfermedad de Charcot-Marie-Tooth/patología , Niño , Preescolar , Creatina Quinasa/sangre , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Miopatías Estructurales Congénitas/sangre , Miopatías Estructurales Congénitas/diagnóstico por imagen , Miopatías Estructurales Congénitas/patología , República de Corea , Secuenciación del Exoma , Adulto JovenRESUMEN
The kinesin heavy chain isoform 5A (KIF5A) gene, which encodes a microtubule-based motor protein, plays an important role in the transport of organelles in the nerve cells. Mutations in the KIF5A showed a wide phenotypic spectrum from hereditary spastic paraplegia (HSP) to axonal Charcot-Marie-Tooth peripheral neuropathy type 2 (CMT2). This study identified three pathogenic KIF5A mutations in Korean CMT2 patients by whole exome sequencing. Two mutations (p.Arg204Trp and p.Arg280His) were previously reported, but p.Leu558Pro was determined to be a novel de novo mutation. All the mutations were not observed in the healthy controls and were located in highly conserved domains among vertebrate species. The p.Arg204Trp mutation was identified from a CMT2 patient with additional complex phenotypes of HSP, ataxia, fatigability and pyramidal sign, but the p.Arg280His and p.Leu588Pro mutations were identified in each axonal CMT2 patient. The p.Arg204Trp mutation was previously reported in a HSP patient with no CMT symptom. The p.Arg280His mutation was reported in a CMT2 patient, which was similarly with our case. However, it was also once reported in a HSP patient with pes cavus. As the first report in Korea, this study identified three KIF5A mutations as the underlying cause of axonal peripheral neuropathy with or without the HSP phenotype. We confirmed a wide inter- and intra-allelic phenotypic spectrum by the mutations in the KIF5A.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Cinesinas/genética , Paraplejía Espástica Hereditaria/genética , Adolescente , Adulto , Enfermedad de Charcot-Marie-Tooth/fisiopatología , Femenino , Humanos , Cinesinas/metabolismo , Masculino , Mutación , Linaje , Fenotipo , República de Corea , Secuenciación del Exoma/métodosRESUMEN
Mutations in the NEFH gene encoding the heavy neurofilament protein are usually associated with neuronal damage and susceptibility to amyotrophic lateral sclerosis (ALS). Recently, frameshift variants in NEFH (p.Asp1004Glnfs*58 and p.Pro1008Alafs*56) have been reported to be the underlying cause of axonal Charcot-Marie-Tooth disease type 2CC (CMT2CC). The frameshift mutation resulted in a stop loss and translation of a cryptic amyloidogenic element (CAE) encoded by the 3' untranslated region (UTR). This study also identified a de novo c.3015_3027dup frameshift mutation predicting p.Lys1010Glnfs*57 in NEFH from a CMT2 family with an atypical clinical symptom of prominent proximal weakness. This mutation is located near the previously reported frameshift mutations, suggesting a mutational hotspot. Lower limb magnetic resonance imaging (MRI) revealed marked hyperintense signal changes in the thigh muscles compared with those in the calf muscles. Therefore, this study suggests that the stop loss and translational elongations by the 3' UTR of the NEFH mutations may be a relatively frequent genetic cause of axonal peripheral neuropathy with the specific characteristics of proximal dominant weakness.
Asunto(s)
Regiones no Traducidas 3'/genética , Axones/patología , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/fisiopatología , Mutación del Sistema de Lectura/genética , Proteínas de Neurofilamentos/genética , Adulto , Enfermedad de Charcot-Marie-Tooth/patología , Análisis Mutacional de ADN , Femenino , Humanos , Extremidad Inferior/diagnóstico por imagen , Imagen por Resonancia Magnética , Conducción Nerviosa/genética , LinajeRESUMEN
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a condition that affects many parts of the body, particularly the brain and muscles. This study examined a Korean MELAS-like syndrome patient with seizure, stroke-like episode, and optic atrophy. Target sequencing of whole mtDNA and 73 nuclear genes identified compound heterozygous mutations p.R205X and p.L255P in the FASTKD2. Each of his unaffected parents has one of the two mutations, and both mutations were not found in 302 controls. FASTKD2 encodes a FAS-activated serine-threonine (FAST) kinase domain 2 which locates in the mitochondrial inner compartment. A FASTKD2 nonsense mutation was once reported as the cause of a recessive infantile mitochondrial encephalomyopathy. The present case showed relatively mild symptoms with a late onset age, compared to a previous patient with FASTKD2 mutation, implicating an inter-allelic clinical heterogeneity. Because this study is the second report of an autosomal recessive mitochondrial encephalomyopathy patient with a FASTKD2 mutation, it will extend the phenotypic spectrum of the FASTKD2 mutation.
Asunto(s)
Heterocigoto , Síndrome MELAS/genética , Mutación , Proteínas Serina-Treonina Quinasas/genética , Adolescente , Adulto , ADN Mitocondrial/química , ADN Mitocondrial/genética , Femenino , Humanos , Lactante , Síndrome MELAS/patología , Masculino , Análisis de Secuencia de ADN , SíndromeRESUMEN
This study aimed to investigate the optimal transducer level for accurate measurement of atrial and pulmonary arterial pressures in the supine position for patients with functional single ventricle. Contrast-enhanced chest computed tomographic images of 108 patients who underwent either the bidirectional cavopulmonary shunt (BCPS) placement or the Fontan procedure were reviewed. Vertical distances from the skin of the back to the uppermost levels of fluid in the single atrium or the pulmonary artery confluence and their ratios to the greatest anteroposterior (AP) diameter of the thoracic cage were determined. In patients who underwent BCPS, the ratios of the uppermost levels of blood in the atrium and pulmonary artery confluence to the greatest AP diameter of the thorax were 76.0 ± 8.1 and 56.3 ± 5.5 %, respectively. The distance (mm) between these two levels was calculated as 24.2 + 0.31 × age (years) (r 2 = 0.08, P < 0.03). In patients who underwent the Fontan procedure, the ratios were 79.3 ± 10.0 and 58.3 ± 5.8 %, respectively. The distance (mm) between these two levels was calculated as 31.1 + 0.44 × age (years) (r 2 = 0.05, P < 0.11). The optimal transducer levels for measuring atrial and pulmonary arterial pressures in the supine position are 75-80 and 55-60 % of the AP diameter of the thorax, respectively, in patients with functional single ventricle. We should consider the difference of the pressure when atrial and pulmonary arterial pressures were measured with the same level of transducers.
Asunto(s)
Atrios Cardíacos/diagnóstico por imagen , Cardiopatías Congénitas/diagnóstico por imagen , Ventrículos Cardíacos/anomalías , Arteria Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adolescente , Presión Arterial/fisiología , Niño , Preescolar , Medios de Contraste , Femenino , Procedimiento de Fontan/métodos , Atrios Cardíacos/cirugía , Cardiopatías Congénitas/cirugía , Ventrículos Cardíacos/cirugía , Humanos , Aumento de la Imagen/métodos , Lactante , Masculino , Arteria Pulmonar/cirugía , Estudios Retrospectivos , Posición Supina , TransductoresRESUMEN
Laboratory tests for herpes zoster (HZ) are required to confirm varicella zoster virus (VZV) infection, especially when a skin lesion is not typical or apparent. The serological test for VZV IgM antibody is simple and cost-effective; however, the change in the VZV IgM-positive rate over the time course of the disease has not been investigated. Therefore, we conducted an observational study to evaluate the positive rate of VZV IgM results during the time course of HZ and estimate the VZV IgM-positive period.After obtaining serum from patients with typical HZ, the VZV IgM titer was examined using enzyme-linked immunosorbent assay methods. After logarithmic transformation of the VZV IgM titer and the period after the onset of HZ, regression analysis was performed with the 2 transformed variables.A total of 62 patients were included in this study, and VZV IgM antibody was positive only in 23 patients (37%). The estimated antibody-positive period after HZ onset was 3.5 weeks (95% confidence interval 2.8-4.6 weeks).These findings suggest that the serological diagnosis of VZV IgM to confirm HZ is only useful within 3.5 weeks after the onset of symptoms.
Asunto(s)
Anticuerpos Antivirales/inmunología , Herpes Zóster/inmunología , Herpesvirus Humano 3/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Herpes Zóster/diagnóstico , Humanos , Inmunoglobulina M/inmunología , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
BACKGROUND: Epidural steroid injection (ESI) is one of the most common procedures for patients presenting low back pain and radiculopathy. However, there is no clear consensus on what constitutes appropriate steroid use for ESIs. To investigate optimal steroid injection methods for ESIs, surveys were sent to all academic pain centers and selected private practices in Korea via e-mail. METHODS: Among 173 pain centers which requested the public health insurance reimbursements for their ESIs and were enrolled in the Korean Pain Society, 122 completed questionnaires were returned, for a rate of 70.5%; also returned were surveys from 39 academic programs and 85 private practices with response rates of 83.0% and 65.9%, respectively. RESULTS: More than half (55%) of Korean pain physicians used dexamethasone for ESIs. The minimum interval of subsequent ESIs at the academic institutions (3.1 weeks) and the private practices (2.1 weeks) were statistically different (P = 0.01). CONCLUSIONS: Although there was a wide range of variation, there were no significant differences between the academic institutions and the private practices in terms of the types and single doses of steroids for ESIs, the annual dose of steroids, or the limitations of doses in the event of diabetes, with the exception of the minimum interval before the subsequent ESI.