Abstract:
OBJECTIVE:The aim of this study was to evaluate if urinary sediment cells offered a robust alternative to muscle biopsy for the diagnosis of single mtDNA deletions. METHODS:Eleven adult patients with progressive external ophthalmoplegia and a known single mtDNA deletion were investigated. Urinary sediment cells were used to isolate DNA, which was then subjected to long-range polymerase chain reaction. Where available, the patient`s muscle DNA was studied in parallel. Breakpoint and thus deletion size were identified using both Sanger sequencing and next generation sequencing. The level of heteroplasmy was determined using quantitative polymerase chain reaction. RESULTS:We identified the deletion in urine in 9 of 11 cases giving a sensitivity of 80%. Breakpoints and deletion size were readily detectable in DNA extracted from urine. Mean heteroplasmy level in urine was 38% ± 26 (range 8 - 84%), and 57% ± 28 (range 12 - 94%) in muscle. While the heteroplasmy level in urinary sediment cells differed from that in muscle, we did find a statistically significant correlation between these two levels (R = 0.714, P = 0.031(Pearson correlation)). INTERPRETATION:Our findings suggest that urine can be used to screen patients suspected clinically of having a single mtDNA deletion. Based on our data, the use of urine could considerably reduce the need for muscle biopsy in this patient group.
journal_name
Ann Clin Transl Neuroljournal_title
Annals of clinical and translational neurologyauthors
Varhaug KN,Nido GS,de Coo I,Isohanni P,Suomalainen A,Tzoulis C,Knappskog P,Bindoff LAdoi
10.1002/acn3.51119subject
Has Abstractpub_date
2020-08-01 00:00:00pages
1318-1326issue
8issn
2328-9503journal_volume
7pub_type
杂志文章abstract:Objective:We aimed to study the occurrence and development of axonal pathology and the influence of astrocytes in vanishing white matter. Methods:Axons and myelin were analyzed using electron microscopy and immunohistochemistry on Eif2b4 and Eif2b5 single- and double-mutant mice and patient brain tissue. In addition, ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.540
更新日期:2018-03-01 00:00:00
abstract::The maintenance of mitochondrial DNA (mtDNA) relies on proteins encoded by nuclear genes. Mutations in their coding sequences result in heterogenous clinical presentations featuring mtDNA instability in affected tissues. DNA2 is a multi-catalytic protein involved in the removal of single strand DNA during mtDNA replic...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50888
更新日期:2019-09-01 00:00:00
abstract:OBJECTIVE:To examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), or their ratio (ApoB/A1) were associated with early changes in cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology in elderly adults with subjective cognitive decline (SCD). METHODS:This study included 507 objectiv...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51153
更新日期:2020-10-01 00:00:00
abstract:INTRODUCTION:The brittle response (BR) in patients with Parkinson's disease (PD) refers to a special type of levodopa-induced dyskinesia (LID). This study aimed to describe the clinical characteristics of BR patients and to analyze the associated risk factors. METHODS:A retrospective study was conducted to analyze the...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51028
更新日期:2020-05-01 00:00:00
abstract:OBJECTIVE:To assess the predictive potential of the complete response pattern from the University of Pennsylvania Smell Identification Test for the diagnosis of Parkinson's disease. METHODS:We analyzed a large dataset from the Arizona Study of Aging and Neurodegenerative Disorders, a longitudinal clinicopathological s...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.447
更新日期:2017-09-08 00:00:00
abstract:OBJECTIVE:To determine the frequency of distinctive EGFr cysteine altering NOTCH3 mutations in the 60,706 exomes of the exome aggregation consortium (ExAC) database. METHODS:ExAC was queried for mutations distinctive for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASI...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.344
更新日期:2016-09-28 00:00:00
abstract:Objective:The dominant model of cognitive impairment in focal epilepsy has emphasised structural bases for cognitive deficits. Current theories of cognition in the healthy brain emphasise the importance of the reweighting of brain network interactions in support of task performance. Here, we explore the hypothesis that...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.503
更新日期:2017-11-24 00:00:00
abstract:OBJECTIVE:Brain connectivity at rest is altered in temporal lobe epilepsy (TLE), particularly in "hub" areas such as the posterior default mode network (DMN). Although both functional and anatomical connectivity are disturbed in TLE, the relationships between measures as well as to seizure frequency remain unclear. We ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.173
更新日期:2015-04-01 00:00:00
abstract:OBJECTIVES:The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and functi...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.384
更新日期:2017-01-16 00:00:00
abstract:BACKGROUND:Frontotemporal dementia (FTD) is associated with complex changes in eating behavior and metabolism, which potentially affect disease pathogenesis and survival. It is currently not known if body composition changes and changes in fat deposition also exist in FTD, the relationship of these changes in eating be...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50869
更新日期:2019-09-01 00:00:00
abstract::Mutations in RNF216 have been found to be associated with autosomal recessive Huntington-like disorder. Here, we describe a patient with Huntington-like disorder caused by a novel de novo RNF216 mutation. The patient started to have choreatic movements of both hands, slowly progressing to head, face, and four extremit...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51047
更新日期:2020-05-01 00:00:00
abstract:OBJECTIVE:To describe the clinical and genetic features of two patients with different phenotypes due to various Dynactin 1 (DCTN1) gene mutations and further explore the phenotype-genotype relationship. METHODS:Patient 1 is a 23-year-old man with congenital foot deformity and life-long distal muscle weakness and atro...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50985
更新日期:2020-02-01 00:00:00
abstract:OBJECTIVE:The mechanism of action of anti-B cell therapy in multiple sclerosis (MS) is not fully understood. Here, we compared the effect of anti-CD20 therapy on microglial activation in two distinct focal rat models of MS. METHODS:The effect of anti-CD20 therapy on lesion formation and extralesional microglial activa...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.94
更新日期:2014-09-01 00:00:00
abstract:Objective:Intracerebral hemorrhage carries a high mortality and survivors are frequently left with significant disability. Immunological mechanisms may play an important role in hemorrhage-induced brain injury, however, research linking these mechanisms with clinical outcome remains limited. We aim to identify serum in...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.595
更新日期:2018-07-03 00:00:00
abstract:OBJECTIVE:Pathogenic variants in SCN8A, encoding the voltage-gated sodium (Na+) channel α subunit Nav1.6, is a known cause of epilepsy. Here, we describe clinical and genetic features of all patients with SCN8A epilepsy evaluated at a single-tertiary care center, with biophysical data on identified Nav1.6 variants and ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50839
更新日期:2019-08-01 00:00:00
abstract::Aicardi-Goutières syndrome is a leukoencephalopathy with calcifications and increased cerebrospinal fluid interferon-α. The relation between interferon-α and brain pathology is poorly understood. We report a patient with mutations in the disease-associated gene SAMHD1. Neuropathology showed an extensive microangiopath...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.213
更新日期:2015-07-01 00:00:00
abstract:Objective:The genetic bases of Alzheimer's disease remain uncertain. An international effort to fully articulate genetic risks and protective factors is underway with the hope of identifying potential therapeutic targets and preventive strategies. The goal here was to identify and characterize the frequency and impact ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.582
更新日期:2018-05-24 00:00:00
abstract:OBJECTIVE:Gaucher disease (GD) is a lysosomal storage disease characterized by a deficiency of glucocerebrosidase. Although enzyme-replacement and substrate-reduction therapies are available, their efficacies in treating the neurological manifestations of GD are negligible. Pharmacological chaperone therapy is hypothes...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.292
更新日期:2016-02-02 00:00:00
abstract::We demonstrate the first use of Optically Pumped Magnetoencephalography (OP-MEG) in an epilepsy patient with unrestricted head movement. Current clinical MEG uses a traditional SQUID system, where sensors are cryogenically cooled and housed in a helmet in which the patient's head is fixed. Here, we use a different typ...
journal_title:Annals of clinical and translational neurology
pub_type:
doi:10.1002/acn3.50995
更新日期:2020-03-01 00:00:00
abstract:OBJECTIVE:Serum neurofilament light (sNfL) is a promising new biomarker in multiple sclerosis (MS). We explored the relationship between sNfL and health outcomes and resource use in MS patients. METHODS:MS patients with serum samples and health-outcome measurements collected longitudinally between 2011 and 2016 were a...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51305
更新日期:2021-01-25 00:00:00
abstract:OBJECTIVE:Heterozygous SHANK3 mutations or partial deletions of the long arm of chromosome 22, also known as Phelan-McDermid syndrome, result in a syndromic form of the autism spectrum as well as in global developmental delay, intellectual disability, and several neuropsychiatric comorbidities. The exact pathophysiolog...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50959
更新日期:2020-01-01 00:00:00
abstract::Refractory epilepsy and encephalopathy are frequently encountered in patients with inborn errors of metabolism. We report a case of an 8-year-old girl with history of developmental delay, autism and intractable epilepsy that was found to have a pathogenic variant in CAD. We briefly review the biochemical pathway of CA...
journal_title:Annals of clinical and translational neurology
pub_type:
doi:10.1002/acn3.51257
更新日期:2021-01-01 00:00:00
abstract:OBJECTIVES:Diabetes leads to cognitive impairment and is associated with age-related neurodegenerative diseases including Alzheimer's disease (AD). Thus, understanding diabetes-induced alterations in brain function is important for developing early interventions for neurodegeneration. Low-capacity runner (LCR) rats are...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.86
更新日期:2014-08-01 00:00:00
abstract::Three relatives carrying a t(4;8)(p15.2;p23.2) translocation had juvenile myoclonic epilepsy, self-limited photosensitive occipital epilepsy and migraine with aura. The t(4;8) translocation interrupted the coding sequence of CSMD1 gene and occurred immediately to the 3'UTR of STIM2 gene. STIM2 was overexpressed in the...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51040
更新日期:2020-05-01 00:00:00
abstract:Objectives:The aim of this study was to investigate whether short-term inverse occlusion, combined with moderate physical exercise, could promote the recovery of visual acuity and stereopsis in a group of adult anisometropic amblyopes. Methods:Ten adult anisometropic patients underwent six brief (2 h) training session...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.698
更新日期:2018-12-28 00:00:00
abstract:Objective:Area postrema (AP) syndrome (defined as: nausea and/or emesis and/or singultus at onset of brainstem dysfunction) comprises complex pathophysiologic mechanisms triggered by different entities. The first objective was to assess the frequency of AP syndrome as a clinical feature in brainstem encephalitis (BE). ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.666
更新日期:2018-10-31 00:00:00
abstract:Background and Objective:Hispanics with multiple sclerosis (MS) present younger and more often with optic neuritis (ON) as compared to Whites in the western United States. Regional differences related to Hispanic genetic admixture could be responsible. We investigated the association between global genetic ancestry and...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.646
更新日期:2018-09-23 00:00:00
abstract:Objective:Determining the sequence in which Huntington's disease biomarkers become abnormal can provide important insights into the disease progression and a quantitative tool for patient stratification. Here, we construct and present a uniquely fine-grained model of temporal progression of Huntington's disease from pr...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.558
更新日期:2018-04-02 00:00:00
abstract:OBJECTIVE:Mitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative disorders such as ataxia and Parkinson's disease. We describe an extended Belgian pedigree where seven individuals presented with adult-onset cerebellar ataxia, axonal peripheral ataxic neuropathy, and tremor, in variable c...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.361
更新日期:2016-11-16 00:00:00
abstract::We report six adult patients with Tyrosinaemia type 1 (HT-1) who presented with recurrent porphyria-like neurological crises after discontinuation/interruption of 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione (NTBC) treatment. The crises were life-threatening for some of the patients, with respiratory mus...
journal_title:Annals of clinical and translational neurology
pub_type:
doi:10.1002/acn3.51160
更新日期:2020-09-01 00:00:00