Abstract:
BACKGROUND:The mitochondrial aminoacyl-tRNA synthetase proteins (mt-aaRSs) are a group of nuclear-encoded enzymes that facilitate conjugation of each of the 20 amino acids to its cognate tRNA molecule. Mitochondrial diseases are a large, clinically heterogeneous group of disorders with diverse etiologies, ages of onset, and involved organ systems. Diseases related to mt-aaRS mutations are associated with specific syndromes that affect the central nervous system and produce highly characteristic MRI patterns, prototypically the DARS2, EARS, and AARS2 leukodystrophies, which are caused by mutations in mitochondrial aspartyl-tRNA synthetase, mitochondria glutamate tRNA synthetase, and mitochondrial alanyl-tRNA synthetase, respectively. BODY: The disease patterns emerging for these leukodystrophies are distinct in terms of the age of onset, nature of disease progression, and predominance of involved white matter tracts. In DARS2 and EARS2 disorders, earlier disease onset is typically correlated with more significant brain abnormalities, rapid neurological decline, and greater disability. In AARS2 leukodystrophy cases reported thus far, there is nearly invariable progression to severe disability and atrophy of involved brain regions, often within a decade. Although most mutations are compound heterozygous inherited in an autosomal recessive fashion, homozygous variants are found in each disorder and demonstrate high phenotypic variability. Affected siblings manifest disease on a wide spectrum. CONCLUSION:The syndromic nature and selective vulnerability of white matter tracts in these disorders suggests there may be a shared mechanism of mitochondrial dysfunction to target for study. There is evidence that the clinical variability and white matter tract specificity of each mt-aaRS leukodystrophy depend on both canonical and non-canonical effects of the mutations on the process of mitochondrial translation. Furthermore, different sensitivities to the mt-aaRS mutations have been observed based on cell type. Most mutations result in at least partial retention of mt-aaRS enzyme function with varied effects on the mitochondrial respiratory chain complexes. In EARS2 and AARS2 cells, this appears to result in cumulative impairment of respiration. Mt-aaRS mutations may also affect alternative biochemical pathways such as the integrated stress response, a homeostatic program in eukaryotic cells that typically confers cytoprotection, but can lead to cell death when abnormally activated in response to pathologic states. Systematic review of this group of disorders and further exploration of disease mechanisms in disease models and neural cells are warranted.
journal_name
J Neurodev Disordjournal_title
Journal of neurodevelopmental disordersauthors
Fine AS,Nemeth CL,Kaufman ML,Fatemi Adoi
10.1186/s11689-019-9292-ysubject
Has Abstractpub_date
2019-12-16 00:00:00pages
29issue
1eissn
1866-1947issn
1866-1955pii
10.1186/s11689-019-9292-yjournal_volume
11pub_type
杂志文章,评审abstract::The primary goal of this study was to examine environmental and neuroendocrine factors that convey increased risk for elevated autistic behavior in boys with Fragile X syndrome (FXS). This study involves three related analyses: (1) examination of multiple dimensions of social approach behaviors and how they vary over ...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1007/s11689-009-9028-5
更新日期:2009-12-01 00:00:00
abstract:: Children with specific language impairment (SLI) are thought to have an inherited form of language impairment that spares other developmental domains. SLI shows strong heritability and recent linkage and association studies have replicated results for candidate genes. Regulatory regions of the genes may be involved. ...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/1866-1955-4-27
更新日期:2012-11-24 00:00:00
abstract::Prader-Willi syndrome (PWS) is a genetic imprinting disease that causes developmental and behavioral disturbances resulting from loss of expression of genes from the paternal chromosome 15q11-q13 region. In about 70% of subjects, this portion of the paternal chromosome is deleted, while 25% have two copies of the mate...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1007/s11689-010-9051-6
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:The overall birth prevalence for congenital malformations of the central nervous system (CNS) among Europeans may be as high as 1 in 100 live births. The etiological factors remain largely unknown. The aim of this study was to detect causative copy number variations (CNVs) in fetuses of terminated pregnancie...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-016-9144-y
更新日期:2016-04-15 00:00:00
abstract:BACKGROUND:The DYX5 locus for developmental dyslexia was mapped to chromosome 3 by linkage study of a large Finnish family, and later, roundabout guidance receptor 1 (ROBO1) was implicated as a candidate gene at DYX5 with suppressed expression from the segregating rare haplotype. A functional magnetoencephalographic st...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-016-9136-y
更新日期:2016-01-27 00:00:00
abstract::Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5' un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are ...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1007/s11689-011-9084-5
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:Facial mimicry is crucial in the recognition of others' emotional state. Thus, the observation of others' facial expressions activates the same neural representation of that affective state in the observer, along with related autonomic and somatic responses. What happens, therefore, when someone cannot mimic...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-019-9272-2
更新日期:2019-07-10 00:00:00
abstract::[This corrects the article DOI: 10.1186/s11689-016-9179-0.]. ...
journal_title:Journal of neurodevelopmental disorders
pub_type: 已发布勘误
doi:10.1186/s11689-017-9192-y
更新日期:2017-03-06 00:00:00
abstract::Autism spectrum disorder (ASD) is a behaviourally defined syndrome where the etiology and pathophysiology is only partially understood. In a small proportion of children with the condition, a specific medical disorder is identified, but the causal significance in many instances is unclear. Currently, the medical condi...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1007/s11689-009-9021-z
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Rett syndrome is a neurodevelopmental disorder caused by a mutation in the X-linked MECP2 gene. Individuals with Rett syndrome typically develop normally until around 18 months of age before undergoing a developmental regression, and the disorder can lead to cognitive, motor, sensory, and autonomic dysfuncti...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-019-9275-z
更新日期:2019-07-31 00:00:00
abstract:BACKGROUND:Gaze processing deficits are a seminal, early, and enduring behavioral deficit in autism spectrum disorder (ASD); however, a comprehensive characterization of the neural processes mediating abnormal gaze processing in ASD has yet to be conducted. METHODS:This study investigated whole-brain patterns of neura...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/1866-1955-6-15
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Various techniques in assisted reproductive technology (ART) have been developed as solutions for specific infertility problems. It is important to gain consensual conclusions on the actual risks of neurodevelopmental disorders among children who are born from ART. This study aimed to quantify the relative r...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章,评审
doi:10.1186/s11689-020-09347-w
更新日期:2020-12-13 00:00:00
abstract:BACKGROUND:Individuals with autism spectrum disorder (ASD) show a relative indifference to the human voice. Accordingly, and contrarily to their typically developed peers, adults with autism do not show a preferential response to voices in the superior temporal sulcus; this lack of voice-specific response was previousl...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-017-9194-9
更新日期:2017-04-05 00:00:00
abstract:BACKGROUND:Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avo...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/1866-1955-4-17
更新日期:2012-06-07 00:00:00
abstract:UNLABELLED: BACKGROUND:A previous study reported enhanced psychomotor speed, and subtle but significant cognitive impairments, modulated by age and by mutations in the fragile X mental retardation 1 (FMR1) gene in adult female fragile X premutation carriers (fXPCs). Because male carriers, unlike females, do not have a...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/1866-1955-4-26
更新日期:2012-11-13 00:00:00
abstract::Fragile X syndrome (FXS) is the most common identifiable genetic cause of intellectual disability and autistic spectrum disorders (ASD), with up to 50% of males and some females with FXS meeting criteria for ASD. Autistic features are present in a very high percent of individuals with FXS, even those who do not meet f...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1007/s11689-011-9074-7
更新日期:2011-09-01 00:00:00
abstract::Turner syndrome (TS) is one of the most common sex chromosome abnormalities. Affected individuals often show a unique pattern of cognitive strengths and weaknesses and are at increased risk for a number of other neurodevelopmental conditions, many of which are more common in typical males than typical females (e.g., a...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1007/s11689-011-9089-0
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:The SYNGAP1 gene encodes for a small GTPase-regulating protein critical to dendritic spine maturation and synaptic plasticity. Mutations have recently been identified to cause a breadth of neurodevelopmental disorders including autism, intellectual disability, and epilepsy. The purpose of this work is to def...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-019-9276-y
更新日期:2019-08-08 00:00:00
abstract::To examine brain volumes in substructures associated with the behavioral features of children with FXS compared to children with idiopathic autism and controls. A cross-sectional study of brain substructures was conducted at the first time-point as part of an ongoing longitudinal MRI study of brain development in FXS....
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1007/s11689-009-9009-8
更新日期:2009-03-01 00:00:00
abstract::Activation of maternal stress response systems during pregnancy has been associated with altered postpartum maternal care and subsequent abnormalities in the offspring's brain and behavioral development. It remains unknown, however, whether similar effects may be induced by exposure to immunological stress during preg...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1007/s11689-008-9000-9
更新日期:2009-03-01 00:00:00
abstract:BACKGROUND:Recent studies link autism spectrum disorders (ASD) with an altered balance between excitation and inhibition (E/I balance) in cortical networks. The brain oscillations in high gamma-band (50-120 Hz) are sensitive to the E/I balance and may appear useful biomarkers of certain ASD subtypes. The frequency of g...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-015-9121-x
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Children with autism spectrum disorder (ASD) show marked impairment in social functioning and poor adaptation to new and changing contexts, which may be influenced by underlying regulatory processes. Oxytocin (OT) and cortisol are key neuromodulators of biological and behavioral responses, show a synergistic...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-016-9165-6
更新日期:2016-08-18 00:00:00
abstract:BACKGROUND:Recent advances in understanding molecular and synaptic mechanisms of intellectual disabilities (ID) in fragile X syndrome (FXS) and Down syndrome (DS) through animal models have led to targeted controlled trials with pharmacological agents designed to normalize these underlying mechanisms and improve clinic...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-016-9167-4
更新日期:2016-09-06 00:00:00
abstract:BACKGROUND:Fragile X syndrome (FXS) is a genetic disorder that is highly comorbid with anxiety and autism spectrum disorder (ASD). Elevated negative affect in young children has been associated with increased risk for both anxiety and ASD; however, these relations remain poorly understood in FXS. METHODS:The present p...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-019-9284-y
更新日期:2019-09-13 00:00:00
abstract::Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID). Anxiety and social withdrawal are considered core features of the FXS phenotype, yet there is limited diagnostic evidence of the prevalence of formal anxiety disorders in FXS. This study assessed the prevalence of anxiety disor...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1007/s11689-010-9067-y
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Individuals diagnosed with fragile X syndrome (FXS), the most common known inherited form of intellectual disability, commonly exhibit significant impairments in social gaze behavior during interactions with others. Although this behavior can restrict social development and limit educational opportunities, b...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-018-9243-z
更新日期:2018-08-28 00:00:00
abstract:BACKGROUND:Alcohol related neurodevelopmental disorder (ARND) falls under the umbrella of fetal alcohol spectrum disorder (FASD), but individuals do not demonstrate the facial characteristics associated with fetal alcohol syndrome (FAS), making diagnosis difficult. While attentional problems in ARND are similar to thos...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/1866-1955-4-12
更新日期:2012-05-18 00:00:00
abstract:BACKGROUND:Children with neurodevelopmental disorders (NDDs) exhibit a shared phenotype that involves executive dysfunctions including impairments in mental flexibility (MF). It is of interest to understand if this phenotype stems from some shared neurobiology. METHODS:To investigate this possibility, we used magnetoe...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-019-9280-2
更新日期:2019-08-19 00:00:00
abstract::The paper argues that both evolutionary and genetic approaches to studying the biological foundations of speech and language could benefit from fractionating the problem at a finer grain, aiming not to map genetics to "language"-or even subdomains of language such as "phonology" or "syntax"-but rather to link genetic ...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1007/s11689-011-9097-0
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Perinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy. OBJECTIVES:To asse...
journal_title:Journal of neurodevelopmental disorders
pub_type: 杂志文章
doi:10.1186/s11689-020-09343-0
更新日期:2020-12-16 00:00:00