Abstract:
Importance:Neurologic disorders with isolated symptoms or complex syndromes are relatively frequent among mitochondrial inherited diseases. Recessive RTN4IP1 gene mutations have been shown to cause isolated and syndromic optic neuropathies. Objective:To define the spectrum of clinical phenotypes associated with mutations in RTN4IP1 encoding a mitochondrial quinone oxidoreductase. Design, Setting, and Participants:This study involved 12 individuals from 11 families with severe central nervous system diseases and optic atrophy. Targeted and whole-exome sequencing were performed-at Hospital Angers (France), Institute of Neurology Milan (Italy), Imagine Institute Paris (France), Helmoltz Zentrum of Munich (Germany), and Beijing Genomics Institute (China)-to clarify the molecular diagnosis of patients. Each patient's neurologic, ophthalmologic, magnetic resonance imaging, and biochemical features were investigated. This study was conducted from May 1, 2014, to June 30, 2016. Main Outcomes and Measures:Recessive mutations in RTN4IP1 were identified. Clinical presentations ranged from isolated optic atrophy to severe encephalopathies. Results:Of the 12 individuals in the study, 6 (50%) were male and 6 (50%) were female. They ranged in age from 5 months to 32 years. Of the 11 families, 6 (5 of whom were consanguineous) had a member or members who presented isolated optic atrophy with the already reported p.Arg103His or the novel p.Ile362Phe, p.Met43Ile, and p.Tyr51Cys amino acid changes. The 5 other families had a member or members who presented severe neurologic syndromes with a common core of symptoms, including optic atrophy, seizure, intellectual disability, growth retardation, and elevated lactate levels. Additional clinical features of those affected were deafness, abnormalities on magnetic resonance images of the brain, stridor, and abnormal electroencephalographic patterns, all of which eventually led to death before age 3 years. In these patients, novel and very rare homozygous and compound heterozygous mutations were identified that led to the absence of the protein and complex I disassembly as well as mild mitochondrial network fragmentation. Conclusions and Relevance:A broad clinical spectrum of neurologic features, ranging from isolated optic atrophy to severe early-onset encephalopathies, is associated with RTN4IP1 biallelic mutations and should prompt RTN4IP1 screening in both syndromic neurologic presentations and nonsyndromic recessive optic neuropathies.
journal_name
JAMA Neuroljournal_title
JAMA neurologyauthors
Charif M,Nasca A,Thompson K,Gerber S,Makowski C,Mazaheri N,Bris C,Goudenège D,Legati A,Maroofian R,Shariati G,Lamantea E,Hopton S,Ardissone A,Moroni I,Giannotta M,Siegel C,Strom TM,Prokisch H,Vignal-Clermont C,Derdoi
10.1001/jamaneurol.2017.2065subject
Has Abstractpub_date
2018-01-01 00:00:00pages
105-113issue
1eissn
2168-6149issn
2168-6157pii
2663746journal_volume
75pub_type
杂志文章相关文献
JAMA Neurology文献大全abstract:IMPORTANCE:To provide clinical and genetic diagnoses for patients' conditions, it is important to identify and characterize the different subtypes of spinocerebellar ataxia (SCA). OBJECTIVE:To clinically and genetically characterize a Spanish kindred with pure SCA presenting with altered vertical eye movements. DESIGN...
journal_title:JAMA neurology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamaneurol.2013.2311
更新日期:2013-06-01 00:00:00
abstract:IMPORTANCE:Progressive multifocal leukoencephalopathy results from lytic infection of the glia by the JC polyomavirus (JCV); JCV granule cell neuronopathy is caused by infection with a mutated form of JCV, leading to a shift in viral tropism from the glia to cerebellar granule cells. This shift results in a clinical sy...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2013.4668
更新日期:2014-04-01 00:00:00
abstract::We are at an inflection point in our study of the human genome as it relates to neurodegenerative disease. The sequencing of the human genome, and its associated cataloging of human genetic variation and technological as well as methodological development, introduced a period of rapid gene discovery over the past deca...
journal_title:JAMA neurology
pub_type: 杂志文章,评审
doi:10.1001/jamaneurol.2013.275
更新日期:2013-06-01 00:00:00
abstract:Importance:In Huntington disease (HD), mutation severity is defined by the length of the CAG trinucleotide sequence, a well-known predictor of clinical onset age. The association with disease trajectory is less well characterized. Quantifiable summary measures of trajectory applicable over decades of early disease prog...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2019.2368
更新日期:2019-08-12 00:00:00
abstract:IMPORTANCE:Studies have shown that both high and low blood pressure (BP) may play a role in the etiology of brain atrophy. High BP in midlife has been associated with more brain atrophy later in life, whereas studies in older populations have shown a relation between low BP and more brain atrophy. Yet, prospective evid...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2013.217
更新日期:2013-08-01 00:00:00
abstract:IMPORTANCE:Here we report a family with coexistence of multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS) with hexanucleotide repeat expansions in C9orf72. OBSERVATIONS:A 65-year-old woman had a 2-year history of ataxia with autonomic dysfunction but without motor neuron signs. She was diagnosed as ...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2013.5762
更新日期:2014-06-01 00:00:00
abstract:IMPORTANCE:Apolipoprotein E (APOE) ε4 is an established risk factor for cognitive decline and the development of dementia, but other factors may help to minimize its effects. OBJECTIVE:Using APOE ε4 as an indicator of high risk, we investigated factors associated with cognitive resilience among black and white older a...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2014.3978
更新日期:2015-03-01 00:00:00
abstract:IMPORTANCE:Progressive external ophthalmoplegia (PEO) is a common feature in adults with mitochondrial (mt) DNA maintenance disorders associated with somatic mtDNA deletions in muscle, yet the causal genetic defect in many patients remains undetermined. OBSERVATIONS:Whole-exome sequencing identified a novel, heterozyg...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2014.1753
更新日期:2015-01-01 00:00:00
abstract:Importance:Although endovascular thrombectomy (EVT) in acute ischemic stroke is recommended by guidelines to improve functional recovery, thus far there are insufficient data on its association with mortality. Objective:To identify guideline-relevant trials of EVT vs medical therapy reporting 90-day mortality and perf...
journal_title:JAMA neurology
pub_type: 杂志文章,meta分析
doi:10.1001/jamaneurol.2019.0525
更新日期:2019-07-01 00:00:00
abstract:Importance:Deposition of the pathological α-synuclein (αSynP) in the brain is the hallmark of synucleinopathies, including Parkinson disease (PD), Lewy body dementia (LBD), and multiple system atrophy (MSA). Whether real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA) assays...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2020.3311
更新日期:2020-09-28 00:00:00
abstract:IMPORTANCE:Magnetic resonance imaging markers of incipient cognitive decline among healthy elderly individuals have become important for both clarifying the biological underpinnings of dementia and clinically identifying healthy individuals at high risk of cognitive decline. Even though the role of hippocampal atrophy ...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2013.3263
更新日期:2013-11-01 00:00:00
abstract:IMPORTANCE:Focal cortical dysplasia (FCD), hemimegalencephaly, and megalencephaly constitute a spectrum of malformations of cortical development with shared neuropathologic features. These disorders are associated with significant childhood morbidity and mortality. OBJECTIVE:To identify the underlying molecular cause ...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2016.0363
更新日期:2016-07-01 00:00:00
abstract:IMPORTANCE:Blast injury has been identified as the signature injury in the conflicts in Iraq and Afghanistan. However it remains to be determined whether fundamental differences may exist between blast-related traumatic brain injury (TBI) and TBI due to other mechanisms. OBJECTIVES:To determine similarities and differ...
journal_title:JAMA neurology
pub_type: 临床试验,杂志文章
doi:10.1001/jamaneurol.2014.1114
更新日期:2014-08-01 00:00:00
abstract:Importance:Early-onset Alzheimer disease (EOAD) is a rare form of Alzheimer disease (AD) with a large genetic basis that is only partially understood. In late-onset AD, elevated circulating cholesterol levels increase AD risk even after adjusting for the apolipoprotein E ε4 (APOE E4) allele, a major genetic factor for ...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2019.0648
更新日期:2019-07-01 00:00:00
abstract:Importance:Identification of genetic factors that interact with the apolipoprotein e4 (APOE4) allele to reduce risk for Alzheimer disease (AD) would accelerate the search for new AD drug targets. Klotho-VS heterozygosity (KL-VSHET+ status) protects against aging-associated phenotypes and cognitive decline, but whether ...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2020.0414
更新日期:2020-07-01 00:00:00
abstract:IMPORTANCE:Despite recessive inheritance, X-linked dystonia-parkinsonism (Lubag disease) has also been described in women presenting with a late-onset isolated parkinsonian syndrome. Interestingly, unlike in other populations, there is a slight female predominance in the prevalence of parkinsonism in the Philippines. ...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2014.56
更新日期:2014-09-01 00:00:00
abstract::A young man with normal neurodevelopment presented with 3 years of medically refractory, progressive epilepsy and myoclonus. Initial examination included neuroimaging, electroencephalography, and biochemical analyses, all of which were unremarkable except for mildly enlarged ventricles. Over the following year, the pa...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2016.3195
更新日期:2017-06-01 00:00:00
abstract:Importance:The central vein sign has been proposed as a specific imaging biomarker for distinguishing between multiple sclerosis (MS) and not MS, mainly based on findings from ultrahigh-field magnetic resonance imaging (MRI) studies. The diagnostic value of the central vein sign in a multicenter setting with a variety ...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2019.2478
更新日期:2019-12-01 00:00:00
abstract:Importance:Apolipoprotein E ε4 (APOEε4) is the single most important genetic risk factor for Alzheimer disease. While APOEε4 is associated with increased amyloid-β burden, its association with cerebral tau pathology has been controversial. Objective:To determine whether APOEε4 is associated with medial temporal tau pa...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2019.4421
更新日期:2020-04-01 00:00:00
abstract:Importance:Although levodopa remains the most effective oral pharmacotherapy for Parkinson disease (PD), its use is often limited by wearing off effect and dyskinesias. Management of such complications continues to be a significant challenge. Objective:To investigate the efficacy and safety of safinamide (an oral amin...
journal_title:JAMA neurology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1001/jamaneurol.2016.4467
更新日期:2017-02-01 00:00:00
abstract:IMPORTANCE:Allogeneic hematopoietic stem cell transplantation (HSCT) has been the only treatment option clinically available during the last 20 years for juvenile metachromatic leukodystrophy (MLD), reported with variable outcome and without comparison with the natural course of the disease. OBJECTIVE:To compare the l...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2016.2067
更新日期:2016-09-01 00:00:00
abstract:IMPORTANCE:Smoking tobacco is a well-established risk factor for multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system usually characterized by bouts and remissions and typically followed by a secondary progressive (SP) course. However, it is not clear whether smoking after diagnosis is...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2015.1788
更新日期:2015-10-01 00:00:00
abstract:IMPORTANCE:β-Amyloid (Aβ) deposition and vascular brain injury (VBI) frequently co-occur and are both associated with cognitive decline in aging. Determining whether a direct relationship exists between them has been challenging. We sought to understand VBI's influence on cognition and clinical impairment, separate fro...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/2013.jamaneurol.405
更新日期:2013-04-01 00:00:00
abstract:IMPORTANCE:This dose-blinded extension of the phase 2 BOLD (BAF312 on MRI Lesion Given Once Daily) Study in relapsing-remitting multiple sclerosis provides evidence on disease activity and safety of a range of siponimod doses for up to 24 months. OBJECTIVE:To assess the safety and efficacy of siponimod for up to 24 mo...
journal_title:JAMA neurology
pub_type: 杂志文章,随机对照试验
doi:10.1001/jamaneurol.2016.1451
更新日期:2016-09-01 00:00:00
abstract:IMPORTANCE:Hematoma volume is the strongest predictor of outcome in intracerebral hemorrhage (ICH). Despite known differences in the underlying biology between deep and lobar ICHs, limited data are available on location specificity of factors reported to affect hematoma volume. OBJECTIVE:To evaluate whether determinan...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2013.98
更新日期:2013-08-01 00:00:00
abstract:IMPORTANCE:While advances have been made in characterizing the C9ORF72 clinical phenotype, the hallmark features that discriminate between carriers and noncarriers remain unclear. OBJECTIVES:To determine the frequency of the C9ORF72 mutation in a frontotemporal dementia (FTD) cohort and to define the clinical, neurops...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2013.6002
更新日期:2014-03-01 00:00:00
abstract:Importance:Scientific and lay interest in negative outcomes associated with exposure to repetitive brain trauma (RBT) continues to strengthen. Concerns about the association between RBT and dementia began more than a century ago, but have resurfaced in the last decade with the more recently described chronic traumatic ...
journal_title:JAMA neurology
pub_type: 杂志文章,评审
doi:10.1001/jamaneurol.2017.2396
更新日期:2017-10-01 00:00:00
abstract:IMPORTANCE:The frequency and distribution of synucleinopathies and tauopathies manifesting with parkinsonism in the general population are poorly understood, thus affecting health care planning and research. OBJECTIVE:To investigate the incidence and distribution of specific types of parkinsonism and related proteinop...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2013.114
更新日期:2013-07-01 00:00:00
abstract:Importance:Prolonged seizures in super-refractory status epilepticus (SRSE) have been shown to cause neuronal death and reorganization, and visual inspection in individual case studies has demonstrated progressive cortical and subcortical atrophy. At present, magnetic resonance imaging (MRI) studies that evaluate brain...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2016.1572
更新日期:2016-10-01 00:00:00
abstract:IMPORTANCE:Fungal meningitis due to injections of contaminated methylprednisolone acetate can present with vascular sequelae in immunocompetent individuals. This is particularly germane to neurologists because better recognition of the clinical characteristics of patients with fungal meningitis and ischemic stroke will...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2013.3586
更新日期:2013-09-01 00:00:00