Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 342
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
PLoS One ; 14(11): e0225656, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31765440

RESUMO

PURPOSE: To assess the clinical utility of next-generation sequencing (NGS) for the diagnosis of patients with optic atrophy (OA). DESIGN: Retrospective cohort study. METHODS: 97 patients were referred to the McMaster University Medical Center (Hamilton, Ontario) for evaluation of bilateral OA. All patients were sent for NGS including a 22 nuclear gene panel and/or complete mitochondrial DNA (mtDNA) sequencing. Positive genetic test results and abnormal vibration sensation were compared in patients +/- environmental exposures or a family history. RESULTS: 19/94 (20.2%) had a positive nuclear variant, of which 15/19 (78.9%) were in the OPA1 gene. No positive mtDNA variants were identified. The detection of a positive genetic variant was significantly different in patients who reported excessive ethanol use, but not in patients who smoke (0/19 (0%) vs. 19/78 (24.4%), P = 0.0164 and 4/22 (18.2%) vs. 15/74 (20.3%), P = 0.829, respectively). Patients with a positive family history were more likely to have a positive genetic variant compared to patients with a negative family history (P = 0.0112). There were significantly more excessive drinkers with an abnormal vibration sensation (P = 0.026), and with a similar trend in smokers (P = 0.074). CONCLUSIONS: All positive genetic variants were identified in nuclear genes. We identified a potential independent pathophysiological link between a history of excessive ethanol consumption and bilateral OA. Further investigations should evaluate and identify potential environmental risk factors for OA.

4.
Appl Physiol Nutr Metab ; 44(12): 1391-1394, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31618598

RESUMO

The legs of 9 men (age 21 ± 2 years, 45 ± 4 mL/(kg·min)) were randomly assigned to complete 6 sessions of high-intensity exercise training, involving either one or four 5-min bouts of counterweighted, single-leg cycling. Needle biopsies from vastus lateralis revealed that citrate synthase maximal activity increased after training in the 4-bout group (p = 0.035) but not the 1-bout group (p = 0.10), with a significant difference between groups post-training (13%, p = 0.021). Novelty Short-term training using brief intense exercise requires multiple bouts per session to increase mitochondrial content in human skeletal muscle.

6.
Am J Physiol Cell Physiol ; 317(5): C894-C899, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31509447

RESUMO

Statins are a cholesterol-lowering drug class that significantly reduce cardiovascular disease risk. Despite their safety and effectiveness, musculoskeletal side-effects, particularly myalgia, are prominent and the most common reason for discontinuance. The cause of statin-induced myalgia is unknown, so defining the underlying mechanism(s) and potential therapeutic strategies is of clinical importance. Here we tested the hypothesis that statin administration activates skeletal muscle system xC-, a cystine/glutamate antiporter, to increase intracellular cysteine and therefore glutathione synthesis to attenuate statin-induced oxidative stress. Increased system xC- activity would increase interstitial glutamate; an amino acid associated with peripheral nociception. Consistent with our hypothesis, atorvastatin treatment significantly increased mitochondrial reactive oxygen species (ROS; 41%) and glutamate efflux (up to 122%) in C2C12 mouse skeletal muscle myotubes. Statin-induced glutamate efflux was confirmed to be the result of system xC- activation, as cotreatment with sulfasalazine (system xC- inhibitor) negated this rise in extracellular glutamate. These findings were reproduced in primary human myotubes but, consistent with being muscle-specific, were not observed in primary human dermal fibroblasts. To further demonstrate that statin-induced increases in ROS triggered glutamate efflux, C2C12 myotubes were cotreated with atorvastatin and various antioxidants. α-Tocopherol and cysteamine bitartrate reversed the increase in statin-induced glutamate efflux, bringing glutamate levels between 50 and 92% of control-treated levels. N-acetylcysteine (a system xC- substrate) increased glutamate efflux above statin treatment alone: up to 732% greater than control treatment. Taken together, we provide a mechanistic foundation for statin-induced myalgia and offer therapeutic insights to alleviate this particular statin-associated side-effect.

7.
Mitochondrion ; 49: 227-231, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31521625

RESUMO

Chronic progressive external ophthalmoplegia (CPEO) is a common presentation of mitochondrial disease. We performed a retrospective evaluation of the molecular genetic testing and genotype-phenotype correlations in a large cohort of adult-onset CPEO patients (N = 111). One hundred percent of patients tested had at least one mitochondrial DNA (mtDNA) deletion. Genetic testing of nuclear genes encoding mitochondrial proteins identified pathogenic/likely pathogenic variants likely to be associated with CPEO in 7.6% of patients. As expected, the nuclear gene most associated with DNA variation was POLG. A single likely pathogenic mitochondrial DNA variant (m.12278T>C) was identified in two unrelated patients. No significant differences were noted in the clinical phenotypes of patients with pathogenic or likely pathogenic nuclear variants in comparison to those with negative nuclear gene testing. Analysis of deletion size and heteroplasmy in muscle-derived mtDNA showed significant correlations with age of symptom onset but not disease severity (number of canonical CPEO features). Results suggest that smaller mtDNA deletions (p = 0.0127, r2 = 0.1201) and higher heteroplasmy of single mtDNA deletions (p = 0.0112, r2 = 0.2483) are associated with an earlier age of onset in CPEO patients.

8.
Can J Neurol Sci ; 46(6): 717-726, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31387656

RESUMO

BACKGROUND: An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care. METHODS: We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities. RESULTS: We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend "mitochondrial cocktails" for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority. CONCLUSIONS: While Canadian physicians' views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.

9.
Obes Rev ; 20(11): 1572-1596, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31410961

RESUMO

Obesity is associated with the production of inflammatory cytokines that are implicated in insulin resistance (IR), and if not addressed, can lead to type 2 diabetes (T2D). The role of the immune system in skeletal muscle (SM) inflammation and insulin sensitivity is not yet well characterized. As SM IR is an important determinant of glycaemia, it is critical that the muscle-immune phenotype is mapped to help design interventions to target T2D. This systematic review synthesized the evidence for SM macrophage content and phenotype in humans and murine models of obesity, and the association of muscle macrophage content and phenotype with IR. Results were synthesized narratively, as we were unable to conduct a meta-analysis. We included 28 studies (n=10 human, n=18 murine), and all studies detected macrophage markers in SM. Macrophage content was positively associated with IR. In humans and mice, there was variability in muscle macrophage content and phenotype in obesity. Overall certainty in the evidence was low due to heterogeneity in detection methods and incompleteness of data reporting. Macrophages are detected in human and murine SM in obesity and a positive association between macrophage content and IR is noted; however, the standardization of markers, detection methods, and reporting of study details is warranted to accurately characterize macrophages and improve the potential for creating specific and targeted immune-based therapies in obesity.

10.
J Child Neurol ; 34(12): 778-781, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31282308

RESUMO

BACKGROUND: WARS2 encodes a tryptophanyl tRNA synthetase, which is involved in mitochondrial protein synthesis. Biallelic mutations in WARS2 are rare and have been associated with a spectrum of clinical presentations, including neurodevelopmental disorder with abnormal movements, lactic acidosis with or without seizures (NEMMLAS). CASE PRESENTATION: Here we present the case of an 8-year-old girl with ataxia and parkinsonism with periventricular white matter abnormalities on magnetic resonance imaging (MRI) and global developmental delay. The initial investigations revealed an elevated lactate level. Extensive metabolic testing, including a muscle biopsy, was inconclusive. Cerebrospinal fluid (CSF) neurotransmitter levels were low; however, a trial of levodopa was unremarkable. The chromosomal microarray and initial ataxia gene panel was normal. Zinc supplementation for a heterozygous variant of unknown significance in the CP gene on the ataxia exome panel was not effective in treating her symptoms. Reanalysis of the ataxia exome panel highlighted biallelic mutations in WARS2, which lead to the diagnosis of neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS). This lead to parental genetic testing, redirected therapy, and helped to expand the symptomology of this rare condition. CONCLUSION: Here we emphasize the importance of imminent and repeat expanded genetic testing to ensure early diagnosis and treatment for rare pediatric disorders. The patient is being trialed on a mitochondrial cocktail in an attempt to compensate for defects in mitochondrial protein synthesis associated with this variant. Longitudinal monitoring of disease manifestation will help establish the currently unknown natural history of this condition.

12.
Spine J ; 19(12): 1911-1916, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31202838

RESUMO

BACKGROUND CONTEXT: Adolescent idiopathic scoliosis (AIS) is the leading cause of spinal deformity in adolescents globally. Recent evidence from genome-wide association studies has implicated variants in or near the ladybird homeobox 1 (LBX1) gene, encoding the ladybird homeobox 1 transcription factor, in AIS development. This gene plays a critical role in guiding embryonic neurogenesis and myogenesis and is vital in muscle mass determination. Despite the confirmation of the role for LBX1 gene variants in the development of AIS, the biological basis of LBX1 contribution to AIS remains mostly unknown. PURPOSE: To investigate the potential role of LBX1 in driving spinal curving, curve laterality, and progression through muscle-based mechanisms in AIS patients by analyzing its gene and protein expression. STUDY DESIGN: This is a cross-sectional study using clinical data and biological samples from the Immunometabolic CONnections to Scoliosis study (ICONS study). PATIENT SAMPLE: Twenty-five patients with AIS provided informed consent. Paraspinal muscle biopsies from the maximal points of concavity and convexity for gene expression and protein analysis were obtained at the start of corrective spinal surgery. OUTCOME MEASURES: The outcome measures included the detection of paraspinal muscle LBX1 mRNA abundance and LBX1 protein expression and the correlation of the latter with age, sex, and curve severity. METHODS: The measurement of mRNA abundance was done using quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, protein lysates from the biopsied muscle samples were probed with a monoclonal LBX1 antibody to compare the muscle protein levels on either side of the scoliotic curve by western blot. This study received funding from the Division of Orthopedics, Department of Surgery, McMaster University, Hamilton, Ontario, Canada ($39,900 CAN for 2 years). The authors have no conflicts of interest to disclose. RESULTS: LBX1 mRNA abundance (concave 2.98±0.87, convex 3.40±1.10, p value 0.73) and protein expression (concave 1.20±0.13, convex 1.21±0.10, p value 0.43) were detected on both sides of the scoliotic curve at equivalent levels. The expression of LBX1 protein did not correlate with age (concave: correlation coefficient 0.32, p value 0.12; convex: correlation coefficient 0.08, p value 0.69), sex (concave: correlation coefficient -0.03, p value 0.08; convex: correlation coefficient 0.07, p value 0.72), or the severity of spinal curving measured using the Cobb angle (concave: correlation coefficient -0.16, p value 0.45; convex: correlation coefficient -0.08, p value 0.69). CONCLUSIONS: LBX1 is expressed in erector spinae muscles, and its levels are equal in muscles on both sides of the scoliotic curve in AIS. The expression of LBX1 on the convex and concave sides of the scoliotic curve did not correlate with age, sex, or the severity of spinal curving. The molecular mechanisms by which LBX1contributes to the development and propagation of AIS need to be explored further in muscle and other tissues.

13.
Neurology ; 92(18): e2109-e2117, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31036580

RESUMO

OBJECTIVE: To investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy. METHODS: UX001-CL301 was a phase 3, double-blind, placebo-controlled, randomized, international study evaluating the efficacy and safety of Ace-ER in patients with GNE myopathy. Participants who could walk ≥200 meters in a 6-minute walk test at screening were randomized 1:1, and stratified by sex, to receive Ace-ER 6 g/d or placebo for 48 weeks and assessed every 8 weeks. The primary endpoint was change in muscle strength over 48 weeks measured by upper extremity composite (UEC) score. Key secondary endpoints included change in lower extremity composite (LEC) score, knee extensor strength, and GNE myopathy-Functional Activity Scale (GNEM-FAS) mobility domain score. Safety assessments included adverse events (AEs), vital signs, and clinical laboratory results. RESULTS: Eighty-nine patients were randomized (Ace-ER n = 45; placebo n = 44). Change from baseline to week 48 for UEC score between treatments did not differ (least square mean [LSM] Ace-ER -2.25 kg vs placebo -2.99 kg; LSM difference confidence interval [CI] 0.74 [-1.61 to 3.09]; p = 0.5387). At week 48, there was no significant difference between treatments for the change in key secondary endpoints: LEC LSM difference (CI) -1.49 (-5.83 to 2.86); knee extension strength -0.40 (-2.38 to 1.58); and GNEM-FAS mobility domain score -0.72 (-2.01 to 0.57). Gastrointestinal events were the most common AEs. CONCLUSIONS: Ace-ER was not superior to placebo in improving muscle strength and function in patients with GNE myopathy. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with GNE myopathy, Ace-ER does not improve muscle strength compared to placebo.

14.
J Neuropathol Exp Neurol ; 78(6): 508-514, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31100146

RESUMO

Mitochondrial diseases (MIDs) involve peripheral nerves and skeletal muscle, but the prevalence of mitochondrial neuropathy is still unclear. Mitochondrial neuropathy has been found to correlate with muscle weakness that may be due to myopathic and/or neurogenic myopathy in patients with MIDs. We examined vastus lateralis muscle biopsies of 58 consecutive patients with mitochondrial myopathy (MM), compared with 204 consecutive non-MM patients. Muscle fiber denervation atrophy was found in 39/58 (67%) of MM patients, significantly more than 41/204 (20%) of non-MM patients and 20/58 (34%) of clinically diagnosed neuropathy. Fiber type grouping was noted in 15/58 (26%) of MM patients, significantly more than 15/204 (7%) of non-MM patients. Type 2 fiber predominance (T2FP) was identified in 7/58 (12%) of MM patients, significantly more than 1/204 (0.5%) of non-MM patients. After dividing patients into age groups, muscle fiber denervation atrophy was significantly more in MM patients aged >50 years than MM patients aged ≤50 years, without differences from all MM patients; there were no differences in fiber type grouping or T2FP between the 2 age groups. Finally, electron microscopy demonstrated MM ultrastructural changes in the neuromuscular junctions. Our findings suggest that a neurogenic component in MM is common.

16.
Front Immunol ; 10: 745, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31024569

RESUMO

Objective: Sporadic Inclusion Body Myositis (sIBM) is an inflammatory myopathy (IIM) without a specific diagnostic biomarker until autoantibodies to the cytosolic 5'-nucleotidase 1A (NT5c1A/Mup44) were reported. The objectives of our study were to determine the sensitivity and specificity of anti-NT5c1A for sIBM, demonstrate demographic, clinical and serological predictors for anti-NT5c1A positivity and determine if anti-nuclear antibody (ANA) indirect immunofluorescence (IIF) staining on HEp-2 cells is a reliable screening method for anti-NT5c1A. Methods: Sera from sIBM patients and controls were stored at -80°C until required for analysis. IgG antibodies to NT5c1A were detected by an addressable laser bead immunoassay (ALBIA) using a full-length human recombinant protein. Autoantibodies to other autoimmune myopathy antigens (Jo-1, OJ, TIF1y, PL-12, SAE, EJ, MDA5, PL7, SRP, NXP2, MI-2) were detected by line immunoassay (LIA), chemiluminescence immunoassay (CIA) or enzyme linked immunosorbent assay (ELISA) and ANA detected by IIF on HEp-2 substrate. Demographic, clinical and serological data were obtained by chart review. Results: Forty-three patients with sIBM, 537 disease control patients with other autoimmune, degenerative and neuromuscular diseases, and 78 healthy controls were included. 48.8% (21/43) of sIBM patients were positive for anti-NT5c1A. The overall sensitivity, specificity, positive predictive value, and negative predictive value of anti-NT5c1A for sIBM were 0.49, 0.92, 0.29, and 0.96, respectively. Compared to sIBM, the frequency of anti-NT5c1A was lower in both the disease control group (8.8%, OR 0.10 [95%CI: 0.05-0.20], p < 0.0001) and in the apparently healthy control group (5.1%, OR 0.06 [95%CI: 0.02-0.18], p < 0.0001). In the univariable analysis, sIBM patients with more severe muscle weakness were more likely to be anti-NT5c1A positive (OR 4.10 [95% CI: 1.17, 14.33], p = 0.027), although this was not statistically significant (adjusted OR 4.30 [95% CI: 0.89, 20.76], p = 0.069) in the multivariable analysis. The ANA of sIBM sera did not demonstrate a consistent IIF pattern associated with anti-NT5c1A. Conclusions: Anti-NT5c1A has moderate sensitivity and high specificity for sIBM using ALBIA. The presence of anti-NT5c1A antibodies may be associated with muscle weakness. Anti-NT5c1A antibodies were not associated with a specific IIF staining pattern, hence screening using HEp-2 substrate is unlikely to be a useful predictor for presence of these autoantibodies.

17.
Mitochondrion ; 47: 139-140, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31026515

RESUMO

We report here on a patient who presented with myasthenia gravis type symptoms (fatigable ptosis, increased jitter on single fiber EMG, and a thymic mass) who was subsequently diagnosed with a mitochondrial myopathy. Sequencing of the mitochondrial genome (mtDNA) identified a transition variant in the tRNA asparagine gene (MT-TN) (m.5728T>C) at in 41% of mtDNA molecules in muscle tissue. The variant was not detectable in blood. The m.5728T>C variant has been reported previously in a ten year old male with global developmental delays, failure to thrive, ataxia, weakness, cognitive regression, seizures, and glomerulosclerosis. The variant was seen in 97% of mtDNA molecules in muscle and 50% in blood. This case report supports the pathogenicity of the m.5728T>C and helps to establish the phenotypic spectrum of this condition at a lower heteroplasmy.

18.
Int J Sport Nutr Exerc Metab ; 29(2): 130-140, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30943823

RESUMO

Ultramarathon running events and participation numbers have increased progressively over the past three decades. Besides the exertion of prolonged running with or without a loaded pack, such events are often associated with challenging topography, environmental conditions, acute transient lifestyle discomforts, and/or event-related health complications. These factors create a scenario for greater nutritional needs, while predisposing ultramarathon runners to multiple nutritional intake barriers. The current review aims to explore the physiological and nutritional demands of ultramarathon running and provide general guidance on nutritional requirements for ultramarathon training and competition, including aspects of race nutrition logistics. Research outcomes suggest that daily dietary carbohydrates (up to 12 g·kg-1·day-1) and multiple-transportable carbohydrate intake (∼90 g·hr-1 for running distances ≥3 hr) during exercise support endurance training adaptations and enhance real-time endurance performance. Whether these intake rates are tolerable during ultramarathon competition is questionable from a practical and gastrointestinal perspective. Dietary protocols, such as glycogen manipulation or low-carbohydrate high-fat diets, are currently popular among ultramarathon runners. Despite the latter dietary manipulation showing increased total fat oxidation rates during submaximal exercise, the role in enhancing ultramarathon running performance is currently not supported. Ultramarathon runners may develop varying degrees of both hypohydration and hyperhydration (with accompanying exercise-associated hyponatremia), dependent on event duration, and environmental conditions. To avoid these two extremes, euhydration can generally be maintained through "drinking to thirst." A well practiced and individualized nutrition strategy is required to optimize training and competition performance in ultramarathon running events, whether they are single stage or multistage.


Assuntos
Desempenho Atlético/fisiologia , Necessidades Nutricionais , Corrida/fisiologia , Fenômenos Fisiológicos da Nutrição Esportiva , Adaptação Fisiológica , Atletas , Carboidratos da Dieta/administração & dosagem , Ingestão de Líquidos , Humanos , Resistência Física
19.
Am J Hum Genet ; 104(4): 685-700, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30929737

RESUMO

Conventional genetic testing of individuals with neurodevelopmental presentations and congenital anomalies (ND/CAs), i.e., the analysis of sequence and copy number variants, leaves a substantial proportion of them unexplained. Some of these cases have been shown to result from DNA methylation defects at a single locus (epi-variants), while others can exhibit syndrome-specific DNA methylation changes across multiple loci (epi-signatures). Here, we investigate the clinical diagnostic utility of genome-wide DNA methylation analysis of peripheral blood in unresolved ND/CAs. We generate a computational model enabling concurrent detection of 14 syndromes using DNA methylation data with full accuracy. We demonstrate the ability of this model in resolving 67 individuals with uncertain clinical diagnoses, some of whom had variants of unknown clinical significance (VUS) in the related genes. We show that the provisional diagnoses can be ruled out in many of the case subjects, some of whom are shown by our model to have other diseases initially not considered. By applying this model to a cohort of 965 ND/CA-affected subjects without a previous diagnostic assumption and a separate assessment of rare epi-variants in this cohort, we identify 15 case subjects with syndromic Mendelian disorders, 12 case subjects with imprinting and trinucleotide repeat expansion disorders, as well as 106 case subjects with rare epi-variants, a portion of which involved genes clinically or functionally linked to the subjects' phenotypes. This study demonstrates that genomic DNA methylation analysis can facilitate the molecular diagnosis of unresolved clinical cases and highlights the potential value of epigenomic testing in the routine clinical assessment of ND/CAs.

20.
Am J Hum Genet ; 104(4): 767-773, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30929741

RESUMO

The diagnostic gap for rare neurodegenerative diseases is still considerable, despite continuous advances in gene identification. Many novel Mendelian genes have only been identified in a few families worldwide. Here we report the identification of an autosomal-dominant gene for hereditary spastic paraplegia (HSP) in 10 families that are of diverse geographic origin and whose affected members all carry unique truncating changes in a circumscript region of UBAP1 (ubiquitin-associated protein 1). HSP is a neurodegenerative disease characterized by progressive lower-limb spasticity and weakness, as well as frequent bladder dysfunction. At least 40% of affected persons are currently undiagnosed after exome sequencing. We identified pathological truncating variants in UBAP1 in affected persons from Iran, USA, Germany, Canada, Spain, and Bulgarian Roma. The genetic support ranges from linkage in the largest family (LOD = 8.3) to three confirmed de novo mutations. We show that mRNA in the fibroblasts of affected individuals escapes nonsense-mediated decay and thus leads to the expression of truncated proteins; in addition, concentrations of the full-length protein are reduced in comparison to those in controls. This suggests either a dominant-negative effect or haploinsufficiency. UBAP1 links endosomal trafficking to the ubiquitination machinery pathways that have been previously implicated in HSPs, and UBAP1 provides a bridge toward a more unified pathophysiology.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA