Abstract:
:The precise genetic cause remains elusive in nearly 50% of patients with presumed neurogenetic disease, representing a significant barrier for clinical care. This is despite significant advances in clinical genetic diagnostics, including the application of whole-exome sequencing and next-generation sequencing-based gene panels. In this study, we identify a deep intronic mutation in the DMD gene in a patient with muscular dystrophy using both conventional and RNAseq-based transcriptome analyses. The implications of our data are that noncoding mutations likely comprise an important source of unresolved genetic disease and that RNAseq is a powerful platform for detecting such mutations.
journal_name
Ann Clin Transl Neuroljournal_title
Annals of clinical and translational neurologyauthors
Gonorazky H,Liang M,Cummings B,Lek M,Micallef J,Hawkins C,Basran R,Cohn R,Wilson MD,MacArthur D,Marshall CR,Ray PN,Dowling JJdoi
10.1002/acn3.267subject
Has Abstractpub_date
2015-12-08 00:00:00pages
55-60issue
1issn
2328-9503pii
ACN3267journal_volume
3pub_type
杂志文章abstract:OBJECTIVE:Examine whether cognitive reserve moderates the association of 1) vascular risk factors and 2) white matter hyperintensity burden with risk of clinical progression and longitudinal cognitive decline. METHODS:BIOCARD Study participants were cognitively normal and primarily middle-aged (M = 57 years) at baseli...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51120
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:The early infantile epileptic encephalopathy type 13 (EIEE13, OMIM #614558) results from de novo missense mutations of SCN8A encoding the voltage-gated sodium channel Nav1.6. More than 20% of patients have recurrent mutations in residues Arg1617 or Arg1872. Our goal was to determine the functional effects of ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.276
更新日期:2015-12-21 00:00:00
abstract:OBJECTIVE:Little is known about the long-term outcome of patients with disorders of consciousness (DOCs) such as unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS). We describe the disease course of a large group of DOC patients 2-14 years after brain damage. METHODS:In 102 patients (59 UWS, 43...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.63
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVE:Friedreich ataxia (FRDA) is the commonest hereditary ataxia in Caucasians. Most patients are homozygous for expanded GAA triplet repeats in the first intron of the frataxin (FXN) gene, involved in mitochondrial iron metabolism. Here, we used magnetoencephalography (MEG) to characterize the main determinants o...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50966
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVE:The objective of this study was to investigate the genetic etiology of the X-linked disorder "Hypomyelination of Early Myelinating Structures" (HEMS). METHODS:We included 16 patients from 10 families diagnosed with HEMS by brain MRI criteria. Exome sequencing was used to search for causal mutations. In silic...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.203
更新日期:2015-06-01 00:00:00
abstract:OBJECTIVE:Multiple sclerosis (MS) is a heterogenous, inflammatory disease of the central nervous system. Microbiota alterations in MS versus healthy controls (HC) are observed, but results are inconsistent. We studied diversity, enterotypes, and specific gut microbial taxa variation between MS and HC, and between MS su...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51004
更新日期:2020-04-01 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:Objective:We aimed to evaluate the impact of underlying mechanism of basilar artery (BA) occlusion on the outcomes after endovascular therapy (EVT) for reperfusion and the outcome factors associated with each mechanism, and to identify radiologic parameters enabling to distinguish the underlying mechanism. Methods:Fro...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.536
更新日期:2018-01-30 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: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:OBJECTIVE:Brain involvement is a serious complication of HIV infection. The earliest changes in the brain, which represents an anatomic site for viral persistence, are largely unknown. METHODS:This investigation used quantitative Magnetic Resonance methodologies, including high resolution and diffusion tensor (DTI) im...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.136
更新日期:2015-01-01 00:00:00
abstract::Biallelic mutations in the sorbitol dehydrogenase (SORD) encoding gene were recently identified as a common genetic cause in autosomal-recessive CMT patients. Here, we investigated the clinical, genetic, and electrophysiological characteristics of three CMT patients with biallelic SORD mutations from a Chinese cohort....
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51268
更新日期:2021-01-01 00:00:00
abstract::Radiation necrosis mostly occurs in and near the radiation field. We used magnetic resonance imaging to study radiation-induced necrosis of atypical onset, severity, and extent following stereotactic radiosurgery for a symptomatic arteriovenous malformation. Susceptibility-sensitive imaging, T1-relaxation, myelin wate...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.704
更新日期:2018-12-10 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::Myotonic dystrophy type I (DM1) is an autosomal dominant disease of which clinical manifestations resemble premature aging. We evaluated the contribution of telomere length in pathogenesis in 361 DM1 patients (12 with serial measurements) and 223 unaffected relative controls using qPCR assay. While no differences in b...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50954
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVES:To assess the impact of ventriculoperitoneal (VPS) in patients with glioma. METHODS:Retrospective review of patients with grade II-IV glioma who had VPS placement from January 1995 to November 2012. RESULTS:We identified 62 patients. At time of VPS, 41 had gait disturbance, 40 cognitive impairment and 16 u...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.17
更新日期:2014-01-01 00:00:00
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: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 u...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51119
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:Human T-cell leukemia virus-1 (HTLV-1) associated myelopathy/tropic spastic paraparesis (HAM/TSP) is induced by chronic inflammation in spinal cord due to HTLV-1 infection. Cerebrospinal fluid (CSF) neopterin or proviral load are clinically measured as disease grading biomarkers, however, they are not exactly...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.169
更新日期:2015-03-01 00:00:00
abstract::T cells and B cells are crucial in the initiation and maintenance of multiple sclerosis (MS), and the activation of these cells is believed to be mediated through specific recognition of antigens by the T- and B-cell receptors. The antigen receptors are highly polymorphic due to recombination (T- and B-cell receptors)...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章,评审
doi:10.1002/acn3.295
更新日期:2016-02-25 00:00:00
abstract::Many observations suggest that mutations of mitochondrial DNA (mtDNA) could be responsible for the neurodegenerative changes of Alzheimer's disease (AD). Here we examined the signal intensity of the four alleles of each mtDNA nucleotide position (np) in whole blood of AD patients and age-matched controls using MitoChi...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.42
更新日期:2014-04-01 00:00:00
abstract:Objective:GDP-mannose pyrophosphorylase B (GMPPB) related phenotype spectrum ranges widely from congenital myasthenic syndrome (CMS), limb-girdle muscular dystrophy type 2T (LGMD 2T) to severe congenital muscle-eye-brain syndrome. Our study investigates the clinicopathologic features of a patient with novel GMPPB mutat...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.787
更新日期:2019-05-08 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: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:Objective:Immunological studies have demonstrated a plethora of beneficial effects of dimethyl fumarate (DMF) on various cell types. However, the cellular and molecular targets are incompletely understood and response markers are scarce. Here, we focus on the relation between nuclear factor (erythroid-derived 2)-like 2...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.553
更新日期:2018-04-16 00:00:00
abstract:Objective:To determine the cognitive profile of adult patients with mitochondrial disease, and the effect of disease severity on cognition. Methods:Using a prospective case-control design, we compared cognition of patients to normative data and to matched controls, assessed three times over 18 months. Forty-nine patie...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.736
更新日期:2019-03-27 00:00:00
abstract::Charcot-Marie-Tooth disease type-1A (CMT1A) is one of the most common types of inherited peripheral nerve diseases. It is caused by the trisomy of chromosome 17p12 (c17p12), a large DNA segment of 1.4 Mb containing PMP22 plus eight other genes. The size of c17p12 is formidable for any cloning technique to manipulate, ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.432
更新日期:2017-06-15 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:The neuropathogenesis of postoperative delirium remains unknown. Low cerebrospinal fluid (CSF) βamyloid protein (Aβ) and high CSF Tau levels are associated with Alzheimer's disease. We therefore assessed whether lower preoperative CSF Aβ/Tau ratio was associated with higher incidence and greater severity of p...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.58
更新日期:2014-05-01 00:00:00