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Bethlem myopathy is one of the collagens VI-related muscular dystrophies caused by mutations in the collagen VI genes. The study was designed to analyze the gene expression profiles in the skeletal muscle of patients with Bethlem myopathy. Six skeletal muscle samples from 3 patients with Bethlem myopathy and 3 control subjects were analyzed by RNA-sequencing. 187 transcripts were significantly differentially expressed, with 157 upregulated and 30 downregulated transcripts in the Bethlem group. Particularly, 1 (microRNA-133b) was considerably upregulated, and 4 long intergenic non-protein coding RNAs, LINC01854, MBNL1-AS1, LINC02609, and LOC728975, were significantly downregulated. We categorized differentially expressed gene using Gene Ontology and showed that Bethlem myopathy is strongly associated with the organization of extracellular matrix (ECM). Kyoto Encyclopedia of Genes and Genomes pathway enrichment reflected themes with significant enrichment of the ECM-receptor interaction (hsa04512), complement and coagulation cascades (hsa04610), and focal adhesion (hsa04510). We confirmed that Bethlem myopathy is strongly associated with the organization of ECM and the wound healing process. Our results demonstrate transcriptome profiling of Bethlem myopathy, and provide new insights into the path mechanism of Bethlem myopathy associated with non-protein coding RNAs.
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Músculo Esquelético , Distrofias Musculares , Humanos , Distrofias Musculares/genética , Perfilación de la Expresión Génica , República de CoreaRESUMEN
A tumor is composed of heterogeneous cell population, which is known as tumor stroma. In particular, blood vessels have an indispensable role in the tumor microenvironment acting as a key player in anti-cancer drug delivery. Recently, efforts have been made to accurately recapitulate the microenvironment by employing distinct cell types, however, the proper formation of perfusable tumor tissue is challenging. Here, perfusable tumor tissue is engineered by implanting multicellular tumor spheroids inside the microfluidic devices. Blood perfusion, spheroid growth, and vascular dynamics were monitored according to the spheroid composition and the contribution of internal and external vascular cells to spheroid perfusion was analyzed. Most notably, the increased penetration depth of fluorescence conjugated anti-cancer drug was observed in tri-culture spheroids. The implementation of tumor microenvironment reconstruction developed in this study not only creates a perfusable tumor vascular model but can also be utilized as a novel drug screening platform with patient-derived samples.
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Antineoplásicos , Neoplasias , Humanos , Esferoides Celulares , Dispositivos Laboratorio en un Chip , Neoplasias/tratamiento farmacológico , Microambiente Tumoral , PerfusiónRESUMEN
OBJECTIVES: Individual variability in nigrostriatal dopaminergic denervation is an important factor underlying clinical heterogeneity in Parkinson's disease (PD). This study aimed to explore whether the pattern of striatal dopamine depletion was associated with white matter (WM) networks in PD. METHODS: A total of 240 newly diagnosed PD patients who underwent 18F-FP-CIT PET scans and brain diffusion tensor imaging at initial assessment were enrolled in this study. We measured 18F-FP-CIT tracer uptake as an indirect marker for striatal dopamine depletion. Factor analysis-derived striatal dopamine loss patterns were estimated in each patient to calculate the composite scores of four striatal subregion factors (caudate, more- and less-affected sensorimotor striata, and anterior putamen) based on the availability of striatal dopamine transporter. The WM structural networks that were correlated with the composite scores of each striatal subregion factor were identified using a network-based statistic analysis. RESULTS: A higher composite score of caudate (i.e., relatively preserved dopaminergic innervation in the caudate) was associated with a strong structural connectivity in a single subnetwork comprising the left caudate and left frontal gyri. Selective dopamine loss in the caudate was associated with strong connectivity in the structural subnetwork whose hub nodes were bilateral thalami and left insula, which were connected to the anterior cingulum. However, no subnetworks were correlated with the composite scores of other striatal subregion factors. The connectivity strength of the network with a positive correlation with the composite score of caudate affected the frontal/executive function either directly or indirectly through the mediation of dopamine depletion in the caudate.
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BACKGROUND AND PURPOSE: This study aimed to identify the epidemiological features of Guillain-Barré syndrome (GBS) in the Korean population. METHODS: Patients with GBS were defined as those who were hospitalized with a primary diagnostic code of G61.0 on the Korean Classification of Disease in a department of neurology, rehabilitation medicine, or pediatrics. We evaluated the incidence and prevalence of GBS as well as physical disability, mortality, and cause of death in patients with GBS from 2002 to 2018 in the Korean population using the Korean National Health Insurance Service database. RESULTS: We identified 11,146 patients with GBS. The ratio of males to females was 1.48. The age-adjusted incidence rate per 100,000 persons increased steadily from 0.84 in 2002 to 1.68 in 2018, as did the age-adjusted prevalence rate per 100,000 persons, from 0.77 to 15.62. The incidence and prevalence of GBS increased with age, peaking at 70-79 years. Among 10,114 patients without physical disability at the time of GBS being diagnosed, 502 (5.0%) patients had moderate disability and 526 (5.2%) had severe disability by the end of the study period. A total of 1,221 (11.0%) patients with GBS died during the mean follow-up period of 17 years (2002-2019). There were 144 (1.3%) in-hospital deaths. CONCLUSIONS: This was the first nationwide epidemiological study of patients with GBS covering the entire population including patients of all ages in the Republic of Korea. We have revealed the seasonality of admissions, disability, and long-term mortality rates in patients with GBS.
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Extracts from the plants Phlomis umbrosa and Dipsacus asperoides-which are widely used in Korean and Chinese traditional medicine to treat osteoarthritis and other bone diseases-were used to treat experimental osteoarthritis (OA) rats. Genome-wide differential methylation regions (DMRs) of these medicinal-plant-treated rats were profiled as therapeutic evidence associated with traditional medicine, and they need to be investigated further using detailed molecular research to extrapolate traditional practices to modern medicine. In total, 49 protein-encoding genes whose expression is differentially regulated during disease progression and recovery have been discovered via systematic bioinformatic analysis and have been approved/proposed as druggable targets for various bone diseases by the US food and drug administration. Genes encoding proteins involved in the PI3K/AKT pathway were found to be enriched, likely as this pathway plays a crucial role during OA progression as well as during the recovery process after treatment with the aforementioned plant extracts. The four sub-networks of PI3K/AKT were highly regulated by these plant extracts. Overall, 29 genes were seen in level 2 (51-75%) DMRs and were correlated highly with OA pathogenesis. Here, we propose that these genes could serve as targets to study OA; moreover, the iridoid and triterpenoid phytochemicals obtained from these two plants may serve as potential therapeutic agents.
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ODFM is a data management system that integrates comprehensive omics information for microorganisms associated with various fermented foods, additive ingredients, and seasonings (e.g. kimchi, Korean fermented vegetables, fermented seafood, solar salt, soybean paste, vinegar, beer, cheese, sake, and yogurt). The ODFM archives genome, metagenome, metataxonome, and (meta)transcriptome sequences of fermented food-associated bacteria, archaea, eukaryotic microorganisms, and viruses; 131 bacterial, 38 archaeal, and 28 eukaryotic genomes are now available to users. The ODFM provides both the Basic Local Alignment Search Tool search-based local alignment function as well as average nucleotide identity-based genetic relatedness measurement, enabling gene diversity and taxonomic analyses of an input query against the database. Genome sequences and annotation results of microorganisms are directly downloadable, and the microbial strains registered in the archive library will be available from our culture collection of fermented food-associated microorganisms. The ODFM is a comprehensive database that covers the genomes of an entire microbiome within a specific food ecosystem, providing basic information to evaluate microbial isolates as candidate fermentation starters for fermented food production.
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Manejo de Datos/métodos , Bases de Datos Genéticas , Alimentos Fermentados/microbiología , Metagenoma , Archaea/genética , Bacterias/genética , Virus/genéticaRESUMEN
BACKGROUND: To investigate the relationship between temporalis muscle thickness (TMT) at baseline as a surrogate marker for sarcopenia and long-term motor outcomes in patients with Parkinson's disease (PD). METHODS: We enrolled 249 patients with drug-naïve early-stage PD (119 males and 130 females, follow-up > 3 years). Baseline TMT of each patient was measured on the axial plane of T1-weighted images. The association between baseline TMT and long-term motor outcomes in PD was assessed using Cox regression models for levodopa-induced dyskinesia, wearing-off, and freezing of gait and a linear mixed model for the longitudinal increases in levodopa-equivalent dose per body weight over time. Statistical analyses were performed separately for sex if an interaction effect between TMT and sex was assumed. RESULTS: TMT differed substantially between the sexes, and male PD patients had higher TMT (6.69 ± 1.39 mm) than female PD patients (5.64 ± 1.34 mm, p < .001). Cox regression models demonstrated that baseline TMT was not associated with the risk of developing levodopa-induced dyskinesia, wearing-off, or freezing of gait during the follow-up period. The linear mixed model was applied separately for sex and demonstrated that higher TMT at baseline was associated with slower increases in levodopa-equivalent dose per body weight in male PD patients, but not in female PD patients. CONCLUSIONS: This study demonstrated that baseline TMT could be an indicator of the longitudinal requirement for dopaminergic medications in male patients with PD, suggesting that sarcopenia may have a detrimental effect on disease progression in PD in a sex-specific manner.
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Discinesias , Trastornos Neurológicos de la Marcha , Músculo Esquelético , Enfermedad de Parkinson , Sarcopenia , Antiparkinsonianos/efectos adversos , Peso Corporal , Discinesias/etiología , Femenino , Trastornos Neurológicos de la Marcha/etiología , Humanos , Levodopa/efectos adversos , Masculino , Músculo Esquelético/fisiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Sarcopenia/diagnóstico por imagen , Sarcopenia/etiologíaRESUMEN
OBJECTIVE: To investigate the association between enlarged perivascular spaces (PVS) in the basal ganglia (BG-PVS) and long-term motor outcomes in Parkinson disease (PD). METHODS: We reviewed the medical records of 248 patients with drug-naive early-stage PD (follow-up >3 years, mean age 67.44 ± 8.46 years, 130 female) who underwent brain MRI and dopamine transporter (DAT) scans at initial assessment. The number of baseline enlarged BG-PVS was counted on axial T2-weighted images. Then, patients were divided into 2 groups: a PD group with a low number (0-10) of enlarged PVS (PD-EPVS-; n = 156) and a PD group with a high number (>10) of enlarged PVS (PD-EPVS+; n = 92). We used Cox regression models to compare the levodopa-induced dyskinesia (LID)-, wearing-off-, and freezing of gait (FOG)-free times between groups. We also compared longitudinal increases in levodopa-equivalent dose per body weight between groups using a linear mixed model. RESULTS: Patients in the PD-EPVS+ group were older (72.28 ± 6.07 years) and had greater small vessel disease burden than those in the PD-EPVS- group (64.58 ± 8.38 years). The PD-EPVS+ group exhibited more severely decreased DAT availability in all striatal subregions except the ventral striatum. The risk of FOG was higher in the PD-EPVS+ group, but the risk of LID or wearing-off was comparable between groups. The PD-EPVS+ group required higher doses of dopaminergic medications for effective symptom control compared to the PD-EPVS- group. CONCLUSION: This study suggests that baseline enlarged BG-PVS can be an indicator of the progression of motor disability in PD.
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Ganglios Basales/patología , Sistema Glinfático/patología , Enfermedad de Parkinson/patología , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Motores/etiología , Trastornos Motores/patología , Enfermedad de Parkinson/complicaciones , PronósticoRESUMEN
This study aimed to compare the patterns of ß-amyloid deposition between patients with early-stage Alzheimer's disease (AD) with mild parkinsonism and those without parkinsonism. Sixty-one patients with early-stage AD (Clinical Dementia Rating [CDR], 0.5 or 1) who underwent 18F-florbetaben (18F-FBB) PET scans were enrolled. We performed comparative analyses of regional FBB uptake in the frontal, parietal, lateral temporal, medial temporal, occipital, anterior cingulate, and posterior cingulate cortices and in the precuneus, striatum, and thalamus between AD patients with mild parkinsonism (AD-p+; n = 23) and those without parkinsonism (AD-p-; n = 38). There was no significant difference in age, sex, years of education, Mini-Mental State Examination score, and white matter hyperintensity severity between groups. The AD-p+ group had lower composite scores in frontal/executive function domain than the AD-p- group. The AD-p+ group had a higher FBB uptake in the occipital cortex, but not in other cortical regions, than the AD-p- group. Our findings suggest that additional ß-amyloid deposition in the occipital region is associated with mild parkinsonism in early-stage AD.
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Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Lóbulo Occipital/metabolismo , Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Femenino , Humanos , Masculino , Lóbulo Occipital/diagnóstico por imagen , Trastornos Parkinsonianos/diagnóstico por imagen , Tomografía de Emisión de Positrones , Índice de Severidad de la EnfermedadRESUMEN
We investigated the clinical, laboratory, and genetic spectra in Korean patients with dysferlinopathy to clarify its genotype-phenotype correlation. We retrospectively reviewed 101 patients from 96 unrelated families with pathogenic variants of DYSF. The most common initial phenotype was Miyoshi myopathy in 50 patients. Median ages at examination and symptom onset were 23 [interquartile range (IQR): 18-30] and 36 years [IQR: 27-48], respectively. We observed 38 variants, including nine novel variants. Four variants (c.2494C > T, c.1284 + 2 T > C, c.663 + 1G > C, and c.2997G > T) in DYSF accounted for 62% of total allele frequencies of pathogenic variants. To analyze the genotype-phenotype correlation, we compared the clinical phenotype between patients with null/null (N/N; n = 55) and null/missense variants (N/M; n = 35). The N/N group had an earlier symptom onset age (median: 20 years [IQR: 17-25]) than the N/M group (median: 29 years [IQR: 23-35], p < .001). Total manual muscle testing scores in lower extremities were lower in the N/N group (median: 80 [IQR: 56-92]) than in the N/M group (median: 89 [IQR: 78-98], p = .013). Our study is the first to report that null variants in DYSF result in an earlier symptom onset than missense variants.
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Miopatías Distales/genética , Disferlina/genética , Variación Genética , Mutación con Pérdida de Función , Atrofia Muscular/genética , Distrofia Muscular de Cinturas/genética , Adolescente , Adulto , Edad de Inicio , Pueblo Asiatico/genética , Análisis Mutacional de ADN , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Tasa de Mutación , Estudios Retrospectivos , Adulto JovenRESUMEN
Mesenchymal stem cells are promising medicine for treating diseases and tissue defects because of their innate ability to secrete therapeutic factors. Intravenous delivery of stem cells, although favored for its minimal invasiveness, is often plagued by low cellular engraftment in the target tissue. To this end, this study hypothesizes that in situ activation of cellular expression of CXC chemokine 4 (CXCR4) would significantly improve cellular migration to injured tissue. This hypothesis was examined by tethering the surface of stem cells with poly(D,L-lactide-co-glycolide)-block-hyaluronic acid (HA) particles containing stromal cell-derived factor-1α, a model chemokine to sensitize CXCR4. The HA blocks in the particles enhanced the association rate constant to stem cells by 3.3-fold, and in turn, increased the number of cells expressing CXCR4 receptors. Consequently, these cells displayed 1.2-fold higher transendothelial migration in vitro and 1.7-fold greater trafficking to the ischemic hindlimb of a mouse than that of the untethered cells.
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Isquemia/metabolismo , Receptores CXCR4/metabolismo , Células Madre/citología , Animales , Quimiocina CXCL12/metabolismo , Miembro Posterior/metabolismo , Cinética , Espectroscopía de Resonancia Magnética , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Células Madre/metabolismoRESUMEN
Dysferlinopathy is an autosomal recessive disease caused by pathogenic variants in DYSF gene. We compared muscle protein extracts from dysferlinopathy patients and control subjects to identify new biomarkers of this myopathy. We reviewed the medical records from January 2002 to October 2016. Eight vastus lateralis muscle samples from five dysferlinopathy patients and three control subjects were selected. We separated proteins/peptides from all eight muscle protein extracts using two-dimensional electrophoresis (2DE). Data were acquired from liquid chromatography-mass spectrometry protein fragmentation patterns after comparing the spot volumes. Western blotting revealed total dysferlin loss in the dysferlinopathy patients but normal expression in the control subjects. 2DE indicated somewhat diverse protein constellations between the dysferlinopathy and control groups. Image analysis showed that 80 spots were differently expressed between two dysferlinopathy and one control samples. We selected 44 spots with consistently different volume between dysferlinopathy and control groups. Liquid chromatography-mass spectrometry indicated 26 differently expressed proteins. Western blotting revealed that creatine kinase M-type, carbonic anhydrase III (muscle specific) and desmin were significantly elevated in dysferlinopathy muscle. Additionally, four proteins (myosin light chain 1/3, skeletal muscle isoform; lamin A/C; ankyrin repeat domain 2; and eukaryotic translation initiation factor 5A-1) were inconsistently elevated in the dysferlinopathy samples. We confirmed the usefulness of the classic biomarker and have newly identified the altered expression of proteins in the skeletal muscles of dysferlinopathy patients.
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Biomarcadores/metabolismo , Músculo Esquelético/metabolismo , Distrofia Muscular de Cinturas/metabolismo , Adolescente , Adulto , Biomarcadores/análisis , Femenino , Humanos , Masculino , Proteínas Musculares/análisis , Proteínas Musculares/metabolismo , Músculo Esquelético/patología , Distrofia Muscular de Cinturas/patología , Proteómica , Adulto JovenRESUMEN
BACKGROUND: Genetic myopathy is a clinically and genetically heterogeneous group of genetic disorders characterized by progressive degeneration of skeletal muscles. Epidemiological studies of genetic myopathy have not yet been performed in Korea. OBJECTIVES: This study used data from the national health insurance claims database to determine the prevalence and socioeconomic status of patients with genetic myopathy in Korea. METHODS: We analyzed the Health Insurance Review and Assessment database from 2007 to 2011. Patients with genetic myopathy were defined based on diagnostic and procedure codes. We then evaluated the prevalence, types of health insurances, and medical expenses of these patients. RESULTS: During the 11-year study period, 2,988 patients with genetic myopathy were enrolled. Among them, 1,762 were men and 1,226 were women. The prevalence per 100,000 population in 2017 was 3.09 (3.94 for men and 2.24 for women). The prevalence of genetic myopathy among men <35 years old (8.33 per 100,000 population) was approximately twice that among women <35 years old (4.06 per 100,000 population). However, there was no significant difference in the prevalence of genetic myopathy among those ≥35 years old according to sex. The ratio of patients using medical aid among all genetic myopathy patients was approximately 4 times than that among the general population in Korea. The medical expenses per person for genetic myopathy increased from USD 2,027 in 2007 to USD 4,810 in 2017. CONCLUSIONS: Our study was the first nationwide epidemiologic study of the prevalence and socioeconomic status of patients with genetic myopathy in Korea. Our results confirmed a sex divergence in a younger population and those with low socioeconomic status among patients with genetic myopathy.
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Enfermedades Musculares/economía , Enfermedades Musculares/genética , Vigilancia de la Población , Clase Social , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Enfermedades Musculares/epidemiología , Vigilancia de la Población/métodos , Prevalencia , República de Corea/epidemiologíaRESUMEN
ADSSL1 myopathy was recently identified as the cause of muscular disorders in Korean patients with distal myopathy. We generated transcriptome profiles of muscles from control subjects and patients with ADSSL1 myopathy. In the present study, RNA sequencing was conducted with seven vastus lateralis muscle samples from four patients with ADSSL1 myopathy and three control subjects. The hierarchical clustering result revealed a separation between myopathy and control groups. A total of 1,260 transcripts were significantly differentially expressed (|fold change|â¯≥â¯2, pâ¯<â¯0.05), with 740 upregulated transcripts and 520 downregulated transcripts in myopathy group. Eighteen transcripts that mapped to purine metabolism pathway were significantly differentially expressed between the two groups, with ten downregulated transcripts and eight upregulated transcripts in myopathy group. In particular, three genes involved in purine nucleotide cycle (ADSSL1, ADSL, and AMPD1) were significantly downregulated in myopathy group. Ten transcripts in glycolysis/gluconeogenesis pathway were also significantly differentially expressed. This is the first study on the altered expression of transcripts in muscle tissues from patients with ADSSL1 myopathy. Our results provide new insights into the pathogenesis of ADSSL1 myopathy.
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Adenilosuccinato Sintasa , Miopatías Distales/genética , Miopatías Distales/metabolismo , Perfilación de la Expresión Génica , Gluconeogénesis/genética , Glucólisis/genética , Músculo Esquelético/metabolismo , Adolescente , Adulto , Femenino , Expresión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia de ARN , Transducción de Señal/genéticaRESUMEN
The rock bream (Oplegnathus fasciatus) is one of the most economically valuable marine fish in East Asia, and due to various environmental factors, there is substantial revenue loss in the production sector. Therefore, knowledge of its genome is required to uncover the genetic factors and the solutions to these problems. In this study, we constructed the first draft genome of O. fasciatus as a reference for the family Oplegnathidae. The genome size is estimated to be 749 Mb, and it was assembled into 766 Mb by combining Illumina and PacBio sequences. A total of 24,053 transcripts (23,338 genes) are predicted, and among those transcripts, 23,362 (97%), are annotated with functional terms. Finally, the completeness of the genome assembly was assessed by CEGMA, which resulted in the complete mapping of 220 (88.7%) core genes in the genome. To the best of our knowledge, this is the first draft genome for the family Oplegnathidae.
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Genoma , Perciformes/genética , AnimalesRESUMEN
Limb-girdle muscular dystrophies (LGMD) are heterogeneous disorders with autosomal inheritance. Autosomal dominant LGMD mapped to 7q36.3 has been classified as LGMD type 1D (LGMD1D) in the Human Gene Nomenclature Committee Database. LGMD1D is characterized predominantly by limb-girdle weakness and may also show a bulbar symptom in some cases. In the past, the frequency of this disease was uncommon, and this disorder was mainly found in Europe and the United States. However, recently, this disorder has been reported in Asia, including Japan, Korea, and Taiwan. Here, we report on three LGMD1D patients, including one with a novel mutation in DNAJB6, c.298T>A. While two patients complained of limb-girdle weakness, as would be expected, one patient had distal weakness. They had various serum creatine kinase levels. Radiologic findings in one patient showed fatty degeneration and atrophy in the posterior part of distal muscles. Pathologic findings in one of the patients showed rimmed vacuoles. Although LGMD1D is still uncommon in Korea, we discovered three Korean patients with LGMD1D, including one novel mutation in DNAJB6, p.Phe100Ile (c.298T>A).
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Proteínas del Choque Térmico HSP40/genética , Imagen por Resonancia Magnética , Chaperonas Moleculares/genética , Debilidad Muscular/diagnóstico por imagen , Distrofia Muscular de Cinturas/diagnóstico por imagen , Distrofia Muscular de Cinturas/genética , Mutación Missense , Proteínas del Tejido Nervioso/genética , Adulto , Creatina Quinasa/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Debilidad Muscular/etiología , Debilidad Muscular/genética , Músculo Esquelético/patología , República de CoreaRESUMEN
To understand the characteristics of ADSSL1 myopathy, we investigated the clinical manifestation in Korean patients with ADSSL1 mutations. We developed a targeted panel of 16 distal-myopathy genes and recruited a total of 12 patients with genetically undetermined distal myopathy. We found four (33%) with ADSSL1 mutations and one (8%) with GNE mutations. ADSSL1 mutations consisted of c.910G>A, c.1048delA and c.1220T>C mutations. Patients with ADSSL1 mutations demonstrated distal muscle weakness in adolescence, followed by quadriceps muscle weakness in the early 30s. All patients had mild facial weakness and two patients complained of easy fatigue while eating and chewing. Vastus lateralis muscle biopsies revealed non-specific chronic myopathic features with a few nemaline rods. Whole body muscle MR imaging showed more fatty replacement in the distal limb and tongue muscles than in the proximal limb and axial muscles. This study showed that ADSSL1 myopathy was not rare among distal myopathy patients of Korean origin, and expanded the clinical and genetic spectrum. Therefore, we suggest that the screening test of ADSSL1 gene should be considered for the diagnosis of distal myopathy.
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Adenilosuccinato Sintasa/genética , Miopatías Distales/genética , Miopatías Distales/fisiopatología , Mutación , Adolescente , Adulto , Pueblo Asiatico/genética , Análisis Mutacional de ADN , Miopatías Distales/diagnóstico por imagen , Miopatías Distales/patología , Femenino , Estudios de Seguimiento , Estudios de Asociación Genética , Humanos , Imagen por Resonancia Magnética , Masculino , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , República de Corea , Estudios Retrospectivos , Imagen de Cuerpo Entero , Adulto JovenRESUMEN
The objective of this study was to investigate the clinical and genetic features of Korean patients with facioscapulohumeral muscular dystrophy type 1 (FSHD), and assessed the impact of molecular defects on phenotypic expression. We enrolled 104 FSHD patients from 87 unrelated Korean families with D4Z4 repeat array of less than 11 copies on 4q35. Sixty-one men and forty-three women were enrolled. Median D4Z4 copy number was 4 units and 99 (95%) Korean patients with FSHD carried 1-6 units. The median age at symptom onset was 13 [interquartile range: 8-17] years old. In 100 symptomatic patients, muscle weakness began in facial muscles in 58 patients, shoulder-girdle muscles in 37, and pelvic-girdle muscles in 5. Disease severity was significantly correlated with D4Z4 copy number. In addition, women were more severely affected than men even though there were no differences in age at examination or in D4Z4 copy number between the two genders. This gender difference among Korean patients was the opposite of analysis on individuals of European ancestry. In conclusion, the present study demonstrated the new diagnostic threshold for FSHD in Koreans based on the D4Z4 repeat array size distribution from 1 to 6 units and expanded the clinical spectrum.
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Dosificación de Gen , Distrofia Muscular Facioescapulohumeral/genética , Distrofia Muscular Facioescapulohumeral/fisiopatología , Caracteres Sexuales , Adulto , Familia , Femenino , Estudios de Asociación Genética , Humanos , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Músculos/patología , Músculos/fisiopatología , Distrofia Muscular Facioescapulohumeral/epidemiología , Distrofia Muscular Facioescapulohumeral/patología , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
PURPOSE: We previously reported that insulin resistance, low high-density lipoprotein (HDL) cholesterol, and glycaemic exposure Index are independently associated with peripheral neuropathy in Korean patients with type 2 diabetes mellitus. We followed the patients who participated in that study in 2006 for another 6 years to determine the relationship between insulin resistance and neuropathy. MATERIALS AND METHODS: This study involved 48 of the original 86 Korean patients with type 2 diabetes mellitus who were referred to the Neurology clinic for the assessment of diabetic neuropathy from January 2006 to December 2006. These 48 patients received management for glycaemic control and prevention of diabetic complications in the outpatient clinic up to 2012. We reviewed blood test results and the nerve conduction study findings of these patients, taken over a 6-year period. RESULTS: Low HDL cholesterol and high triglycerides significantly influenced the development of diabetic neuropathy. Kitt value (1/insulin resistance) in the previous study affected the occurrence of neuropathy, despite adequate glycaemic control with HbA1c <7%. Insulin resistance affected the development of diabetic neuropathy after 6 years: insulin resistance in 2006 showed a positive correlation with a change in sural sensory nerve action potential in 2012. CONCLUSION: Diabetic neuropathy can be affected by previous insulin resistance despite regular glycaemic control. Dyslipidaemia should be controlled in patients who show high insulin resistance because HDL cholesterol and triglycerides are strongly correlated with later development of diabetic neuropathy.