Abstract:
:Hereditary spastic paraplegias (HSPs) are a heterogeneous group of genetic disorders with spastic paraparesis as the main clinical feature. Complex forms may co-occur with other motor, sensory, and cognitive impairment. A growing number of loci and genes are being identified, but still more than 50% of the patients remain without molecular diagnosis. We present a Spanish family with autosomal dominant HSP and intellectual disability (ID) in which we found a possible dual genetic diagnosis with incomplete penetrance and variable expressivity in the parents and three siblings: a heterozygous duplication of 15q11.2-q13.1 found by array CGH and a novel missense heterozygous change in REEP1 [c.73A>G; p.(Lys25Glu)] found by whole exome sequencing (WES). Following the standard genetic diagnosis approach in ID, array CGH analysis was first performed in both brothers affected by spastic paraparesis and ID from school age, and a heterozygous duplication of 15q11.2-q13.1 was found. Subsequently, the duplication was also found in the healthy mother and in the sister, who presented attention deficit/hyperactivity disorder (ADHD) symptoms from school age and pes cavus with mild pyramidal signs at 22 years of age. Methylation analysis revealed that the three siblings carried the duplication unmethylated in the maternal allele, whereas their mother harbored it methylated in her paternal allele. Functional studies revealed an overexpression of UBE3A and ATP10A in the three siblings, and the slightest cognitive phenotype of the sister seems to be related to a lower expression of ATP10A. Later, searching for the cause of HSP, WES was performed revealing the missense heterozygous variant in REEP1 in all three siblings and the father, who presented subtle pyramidal signs in the lower limbs as well as the sister. Our findings reinforce the association of maternally derived UBE3A overexpression with neurodevelopmental disorders and support that a spectrum of clinical severity is present within families. They also reveal that a dual genetic diagnosis is possible in patients with presumed complex forms of HSP and cognitive impairment.
journal_name
Front Neuroljournal_title
Frontiers in neurologyauthors
Aguilera-Albesa S,de la Hoz AB,Ibarluzea N,Ordóñez-Castillo AR,Busto-Crespo O,Villate O,Ibiricu-Yanguas MA,Yoldi-Petri ME,García de Gurtubay I,Perez de Nanclares G,Pereda A,Tejada MIdoi
10.3389/fneur.2020.00041subject
Has Abstractpub_date
2020-02-14 00:00:00pages
41issn
1664-2295journal_volume
11pub_type
abstract::Adolescents with traumatic brain injury (TBI) typically demonstrate good recovery of previously acquired skills. However, higher-order and later emergent cognitive functions are often impaired and linked to poor outcomes in academic and social/behavioral domains. Few control trials exist that test cognitive treatment ...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2014.00087
更新日期:2014-06-11 00:00:00
abstract::The developmental vulnerability of different classes of axonal pathways in preterm white matter is not known. We propose that laminar compartments of the developing cerebral wall serve as spatial framework for axonal growth and evaluate potential of anatomical landmarks for understanding reorganization of the cerebral...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2014.00139
更新日期:2014-07-29 00:00:00
abstract:BACKGROUND:The present review investigated which findings in vascular imaging techniques can be used to predict clinical outcome and the risk of symptomatic intracerebral hemorrhage (sICH) in patients who underwent intravenous thrombolytic treatment. METHODS:Publications were searched, and the inclusion criteria were ...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2016.00077
更新日期:2016-05-18 00:00:00
abstract::Humans evolved a symbiotic relationship with their gut microbiome, a complex microbial community composed of bacteria, archaea, protists, and viruses, including bacteriophages. The enteric nervous system (ENS) is a gateway for the bidirectional communication between the brain and the gut, mostly through the vagus nerv...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2019.00574
更新日期:2019-06-04 00:00:00
abstract::Purpose: The use of optical coherence tomography (OCT) of the retina to detect inner retinal degeneration is being investigated as a potential biomarker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), and an overwhelming body of evidence indicates that discovery of disease-modifying treatments for AD...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2020.578698
更新日期:2020-10-16 00:00:00
abstract::Here, we describe a 79-year-old man, admitted to our unit for worsening diplopia and fatigue, started a few weeks after an episode of bronchitis and flu vaccination. Past medical history includes myasthenia gravis (MG), well-controlled by Pyridostigmine, Azathioprine, and Prednisone. During the first days, the patient...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2019.00823
更新日期:2019-08-13 00:00:00
abstract::With respect to photoreceptor function, it is well known that electroretinogram (ERG) amplitudes decrease with age, but to our knowledge, studies describing age-related changes in the pupil light response (PLR) of mice are lacking. This study recorded the PLR and ERG in C57BL/6 and Sv129S6 wild-type mice at three diff...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00056
更新日期:2019-02-04 00:00:00
abstract::Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the pediatric age group probably linked to the use of the Pandemrix influenza vaccine in 2009, has increased awareness that different environmental f...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2016.00130
更新日期:2016-08-10 00:00:00
abstract::Vestibular impairment has become a frequent consequence following blast-related traumatic brain injury (bTBI) in military personnel and Veterans. Behavioral outcomes such as depression, fear and anxiety are also common comorbidities of bTBI. To accelerate pre-clinical research and therapy developments, there is a need...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.00618
更新日期:2020-07-15 00:00:00
abstract::Chronic idiopathic axonal polyneuropathy (CIAP) is a slowly progressive predominantly sensory axonal polyneuropathy. The prevalence of CIAP increases with age. The pathogenic cause of CIAP is unknown although there are several prevailing etiological hypotheses. In this mini review, we focus on the hypothesis of distur...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2018.00043
更新日期:2018-02-12 00:00:00
abstract::Objective: To evaluate ocular and cervical vestibular evoked myogenic potentials (oVEMPs and cVEMPs) in patients with solely intracochlear localization of an intralabyrinthine schwannoma (ILS). Study Design: Retrospective analysis of a series of cases. Setting: Monocentric study at a tertiary referral center. Patients...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.549817
更新日期:2020-10-27 00:00:00
abstract::Background: Headache associated with Moyamoya disease (HAMD) in the Chinese population is not well-described. The long-term outcome of surgical revascularization and natural course of HAMD has not been disclosed either. Methods: A headache screening questionnaire in China based on the ICHD2 and a face-to-face intervie...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.605636
更新日期:2020-11-26 00:00:00
abstract:BACKGROUND:Persistent postural-perceptual dizziness (PPPD) is a common functional vestibular disorder characterized by persistent symptoms of non-vertiginous dizziness and unsteadiness that are exacerbated by upright posture, self-motion, and exposure to complex or moving visual stimuli. Recent physiologic and neuroima...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2017.00529
更新日期:2017-10-17 00:00:00
abstract::The relationship between circadian rhythm and epilepsy has been recognized for decades. Yet many questions underlying the complex mechanisms of their interaction remain elusive. A better understanding on this topic allows the development of accurate seizure-detection algorithm and alternative precise therapeutic strat...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2020.00751
更新日期:2020-07-24 00:00:00
abstract::Objective: The platelet-to-lymphocyte ratio (PLR) is a new marker of atherosclerotic inflammation and has been identified as a predictive factor in cardiovascular diseases, but its significance in patients with acute ischaemic stroke (AIS) who have undergone intravenous thrombolysis (IVT) is still unknown. Methods: Co...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.01192
更新日期:2019-11-13 00:00:00
abstract::Background and Purpose: A large body of literature reported the association of particulate matter (PM) with stroke in high-income countries. Few studies have examined the association between PM and stroke in middle- and low-income countries and considered the types of stroke. In this study, we examined the short-term ...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.00827
更新日期:2018-10-02 00:00:00
abstract::Localization of the epileptogenic zone (EZ) is crucial in the surgical treatment of focal epilepsy. Recently, EEG studies have revealed that the EZ exhibits abnormal connectivity, which has led investigators to now consider connectivity as a biomarker to localize the EZ. Further, abnormal connectivity of the EZ may pr...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2020.569699
更新日期:2020-11-25 00:00:00
abstract::Noradrenaline, one of the main brain monoamines, has powerful central influences on forebrain neurobiological processes which support the mental activities occurring during the sleep-waking cycle. Noradrenergic neurons are activated during waking, decrease their firing rate during slow wave sleep, and become silent du...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2011.00081
更新日期:2011-12-12 00:00:00
abstract::Background: Glioblastoma (GBM) is the most aggressive type of primary malignant brain tumor. Carmustine is used by intravenous injection or local implantation in the resection cavity for gliomas, including GBMs. However, the therapeutic potential of carmustine is not well-recognized. This analysis aimed to evaluate th...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2020.01036
更新日期:2020-09-17 00:00:00
abstract::For epileptic patients requiring resective surgery, a modality called stereo-electroencephalography (SEEG) may be used to monitor the patient's brain signals to help identify epileptogenic regions that generate and propagate seizures. SEEG involves the insertion of multiple depth electrodes into the patient's brain, e...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.605696
更新日期:2021-01-06 00:00:00
abstract:OBJECTIVE:Effective stroke care does not end with acute treatment during hospitalization, but extends through rehabilitation and secondary stroke prevention. In transitions across care environments, stroke patients are vulnerable to errors in communication of diagnosis and treatment. This study aimed to demonstrate tha...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2015.00227
更新日期:2015-10-27 00:00:00
abstract::While the spread of some neurodegenerative disease-associated proteinopathies, such as tau and α-synuclein, is well studied and clearly implicates transsynaptic pathology transmission, research into the progressive spread of amyloid-β pathology has been less clear. In fact, prior analyses of transregional amyloid-β pa...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2017.00653
更新日期:2017-12-18 00:00:00
abstract:AIMS:To construct and validate a short scale for the assessment of the severity of visual height intolerance (vHI) and acrophobia. METHODS:The questionnaire was developed from two earlier representative epidemiological studies (n = 5,529). Items were applied in a telephone survey of a representative population-based s...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2017.00211
更新日期:2017-06-01 00:00:00
abstract::Numerous studies suggest that the increased activity of p38MAPK plays an important role in the abnormal immune and inflammatory response observed in the course of neurodegenerative diseases such as Alzheimer's disease. On the other hand, high levels of p38MAPK are present in the brain during normal aging, suggesting t...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00675
更新日期:2019-06-25 00:00:00
abstract::Migraine is a chronic disease characterized by unilateral, pulsating, and often moderate-to-severe recurrent episodes of headache with nausea and vomiting. It affects approximately 15% of the general population, yet the underlying pathophysiological mechanisms are not fully understood. Optical coherence tomography (OC...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2017.00684
更新日期:2017-12-13 00:00:00
abstract::Background: The forefront treatment of Parkinson's disease (PD) is Levodopa. When patients are treated with Levodopa cerebral blood flow is increased while cerebral metabolic rate is decreased in key subcortical regions including the putamen. This phenomenon is especially pronounced in patients with Levodopa-induced d...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.01217
更新日期:2019-11-21 00:00:00
abstract:Objective:We investigated the reliability and accuracy of a bedside diagnostic algorithm for patients presenting with vertigo/unsteadiness to the emergency department. Methods:We enrolled consecutive adult patients presenting with vertigo/unsteadiness at a tertiary hospital. STANDING, the acronym for the four-step alg...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2017.00590
更新日期:2017-11-07 00:00:00
abstract:OBJECTIVE:To provide a systematic review of the clinical and radiological features of lesion-induced central positional nystagmus (CPN) and identify salient characteristics that differentiate central from peripheral positional nystagmus (PN). METHODS:Systematic literature search according to the preferred reporting it...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2017.00141
更新日期:2017-04-20 00:00:00
abstract::Background: Chronic progressive neurological diseases like high grade glioma (HGG), Parkinson's disease (PD), and multiple sclerosis (MS) are incurable, and associated with increasing disability including cognitive impairment, and reduced life expectancy. Patients with these diseases have complex care needs. Therefore...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.01157
更新日期:2019-01-14 00:00:00
abstract::Stroke is a leading cause of death and disability worldwide. While various risk factors have been identified, sleep has only been considered a risk factor more recently. Various epidemiologic studies have associated stroke with sleep such as sleep duration, and laboratory and clinical studies have proposed various und...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2017.00392
更新日期:2017-08-08 00:00:00