mutation causes sex-dependent neurologic disorder.

Background: Sex-specific predilection in neurological diseases caused by mutations in autosomal genes is a phenomenon whose molecular basis is poorly understood. We studied females of consanguineous Bedouin kindred presenting with severe global developmental delay and epilepsy.

Methods: Linkage analysis, whole exome sequencing, generation of CRISPR/cas9 knock-in mice, mouse behaviour and molecular studies RESULTS: Linkage analysis and whole exome sequencing studies of the affected kindred delineated a ~5 Mbp disease-associated chromosome 2q35 locus, containing a novel homozygous frameshift truncating mutation in , in line with recent studies depicting similar putative loss-of-function human phenotypes with female preponderance.

Direct and Indirect Predictors of Burden in Arab-Bedouin and Jewish-Israeli Mothers Caring for a Child with Epilepsy.

Objective: Caring for a child with epilepsy poses various psychological, physical and medical challenges; these can lead to caregiver burden. The aim of this study was to identify predictors of burden with mothers caring for a child with epilepsy. Our analyses included sociodemographic (e.

Correlates of Caregiving Burden among Bedouin-Muslim Mothers of Children Diagnosed with Epilepsy.

Unlabelled: A paucity of research exists on caregiving burden (CB) and the factors associated with it among minority groups, such as Bedouin mothers of children diagnosed with epilepsy (CDE). The aim of this study was to explore associations between CB and care-recipients' characteristics, contextual factors, and caregivers' characteristics among those mothers.

Methods: A total of 50 mothers completed self-report questionnaires while visiting pediatric neurology outpatient clinic centers, using valid and reliable measures.

PSMC1 variant causes a novel neurological syndrome.

Proteasome 26S, the eukaryotic proteasome, serves as the machinery for cellular protein degradation. It is composed of the 20S core particle and one or two 19S regulatory particles, composed of a base and a lid. To date, several human diseases have been associated with mutations within the 26S proteasome subunits; only one of them affects a base subunit.

Phenotypic variability and mutation hotspot in COX15-related Leigh syndrome.

COX15 mutations were shown to underlie Leigh syndrome (LS), a progressive subacute necrotizing encephalopathy caused by defects in the mitochondrial respiratory chain. Here, two siblings of consanguineous kindred presented in infancy with a syndrome of hypotonia, nystagmus, psychomotor retardation, and pyramidal signs. Toward the end of their second year, both patients developed progressive quadriparesis, convulsions, and pseudobulbar palsy.

Correlates of quality of life in mothers of children with diagnosed epilepsy.

Contrary to a plethora of studies on the quality of life (QoL) of parents caring for children with chronic conditions, information regarding parents of children with epilepsy remains limited. The main purpose of the current study was to explore associations between children's biomedical characteristics, mothers' sociodemographic characteristics, mothers' situational factors, and QoL among mothers of children with epilepsy. One hundred and fifty mothers of children with epilepsy completed valid and reliable measures.

mutation affects ER homeostasis, causing a neurological syndrome.

Background: Consanguineous kindred presented with an autosomal recessive syndrome of intrauterine growth retardation, marked developmental delay, spastic quadriplegia with profound contractures, pseudobulbar palsy with recurrent aspirations, epilepsy, dysmorphism, neurosensory deafness and optic nerve atrophy with no eye fixation. Affected individuals died by the age of 4. Brain MRI demonstrated microcephaly, semilobar holoprosencephaly and agenesis of corpus callosum.

Novel SBF1 splice-site null mutation broadens the clinical spectrum of Charcot-Marie-Tooth type 4B3 disease.

Four siblings of consanguineous Bedouin kindred presented at infancy with an autosomal recessive syndrome of congenital microcephaly, facial dysmorphism, strabismus, developmental delay and ataxia with positive pyramidal signs. Toward the end of their first decade, they developed areflexia, multiple cranial neuropathies and severe polyneuropathy with progressive muscle weakness, affecting proximal and distal extremities. Physical assessment exhibited kyphoscoliosis, bilateral syndactyly and distal muscle wasting with drop-foot and pes cavus.

RSRC1 mutation affects intellect and behaviour through aberrant splicing and transcription, downregulating IGFBP3.

RSRC1, whose polymorphism is associated with altered brain function in schizophrenia, is a member of the serine and arginine rich-related protein family. Through homozygosity mapping and whole exome sequencing we show that RSRC1 mutation causes an autosomal recessive syndrome of intellectual disability, aberrant behaviour, hypotonia and mild facial dysmorphism with normal brain MRI. Further, we show that RSRC1 is ubiquitously expressed, and that the RSRC1 mutation triggers nonsense-mediated mRNA decay of the RSRC1 transcript in patients' fibroblasts.

Temporal lobe surgery for intractable epilepsy in children: What to do with the hippocampus?

Purpose: Resection of the hippocampus can cause verbal memory decline, especially in the pediatric population. Thus, preservation of the hippocampus can be crucial for the quality of life of children with intractable temporal lobe epilepsy (TLE) who are candidates for epilepsy surgery. We investigated techniques that determine whether the hippocampus is part of the epileptogenic zone and the outcomes of pediatric surgery aimed to spare the hippocampus.

Progressive hereditary spastic paraplegia caused by a homozygous KY mutation.

Twelve individuals of consanguineous Bedouin kindred presented with autosomal recessive progressive spastic paraplegia evident as of age 0-24 months, with spasticity of lower limbs, hyperreflexia, toe walking and equinus deformity. Kyphoscolisois was evident in older patients. Most had atrophy of the lateral aspects of the tongue and few had intellectual disability.

SLC30A9 mutation affecting intracellular zinc homeostasis causes a novel cerebro-renal syndrome.

A novel autosomal recessive cerebro-renal syndrome was identified in consanguineous Bedouin kindred: neurological deterioration was evident as of early age, progressing into severe intellectual disability, profound ataxia, camptocormia and oculomotor apraxia. Brain MRI was normal. Four of the six affected individuals also had early-onset nephropathy with features of tubulo-interstitial nephritis, hypertension and tendency for hyperkalemia, though none had rapid deterioration of renal function.

Therapy with eculizumab for patients with CD59 p.Cys89Tyr mutation.

Objective: The objective of this work was to report on the outcome of eculizumab treatment in pediatric patients with recurrent acute predominantly motor, demyelinating neuropathy with conduction block, and chronic hemolysis attributed to p.Cys89Tyr mutation in the CD59 gene.

Methods: Four patients were recruited from our new registry of patients with homozygosity for the p.

New DSM-5 criteria for ADHD - Does it matter?

Objective: The new Diagnostic Statistical Manual (DSM) requires the presence of fewer symptoms to make a diagnosis of adult ADHD while the criteria for diagnosis in childhood are unchanged as compared to previous editions. This study examines the prevalence of adults meeting the revised DSM-5 symptoms cutoff as compared to the previous DSM-IV symptoms cutoff.

Method: This study is part of a larger nationwide study that evaluated the use of, and the attitudes toward, ADHD medications by university students.

Multiplex families with epilepsy: Success of clinical and molecular genetic characterization.

Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis.

Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis.

CDC174, a novel component of the exon junction complex whose mutation underlies a syndrome of hypotonia and psychomotor developmental delay.

Siblings of non-consanguineous Jewish-Ethiopian ancestry presented with congenital axial hypotonia, weakness of the abducens nerve, psychomotor developmental delay with brain ventriculomegaly, variable thinning of corpus callosum and cardiac septal defects. Homozygosity mapping identified a single disease-associated locus of 3.5 Mb on chromosome 3.

A syndrome of congenital microcephaly, intellectual disability and dysmorphism with a homozygous mutation in FRMD4A.

A consanguineous Bedouin Israeli kindred presented with a novel autosomal recessive intellectual disability syndrome of congenital microcephaly, low anterior hairline, bitemporal narrowing, low-set protruding ears, strabismus and tented thick eyebrows with sparse hair in their medial segment. Brain imaging demonstrated various degrees of agenesis of corpus callosum and hypoplasia of the vermis and cerebellum. Genome-wide linkage analysis followed by fine mapping defined a 7.

Blood-brain barrier dysfunction can contribute to pharmacoresistance of seizures.

Objective: We tested the hypothesis that interstitial albumin can contribute to pharmacoresistance, which is common among patients with focal epilepsies. These patients often present with an open blood-brain barrier (BBB), resulting in diffusion of drug-binding albumin into the brain interstitial space.

Methods: Seizure-like events (SLEs) induced by 100 μm 4-aminopyridine (4-AP) were monitored using extracellular field potential recordings from acute rat entorhinal cortex-hippocampus slices.

Validation of actigraphy with continuous video-electroencephalography in children with epilepsy.

Background: The relationship between epilepsy and sleep is bidirectional as seizures disrupt sleep and coexisting sleep disorders have detrimental effects on seizure control and quality of life for both the children and their families. Previous research has reported on sleep disturbance in children with epilepsy primarily by subjective parental reports. Actigraphy may provide a more accurate objective evaluation of sleep, but the validity of this sleep measure for children with epilepsy has not yet been assessed.

A novel mutation in SCN9A in a child with congenital insensitivity to pain.

Background: [corrected] Congenital insensitivity to pain (CIP) is a rare condition in which patients have no pain perception and anosmia but are otherwise essentially normal (OMIM 243000). The recent discovery of the genetic defects underlying 3 monogenic pain disorders has provided additional and important insights about some components of human pain. Genetic studies in families demonstrating recessively inherited channelopathy-associated insensitivity to pain have identified nonsense mutations that result in truncation of the voltage-gated sodium channel type IX subunit (SCN9A), a 113.

PRRT2 mutations: exploring the phenotypical boundaries.

Background: Mutations in the proline-rich transmembrane protein 2 (PRRT2) gene have been identified in patients with benign (familial) infantile convulsions (B(F)IC), infantile convulsions with choreoathetosis (ICCA) and paroxysmal dyskinesias (PDs). However it remains unknown whether PRRT2 mutations are causal in other epilepsy syndromes. After we discovered a PRRT2 mutation in a large family with ICCA containing one individual with febrile seizures (FS) and one individual with West syndrome, we analysed PRRT2 in a heterogeneous cohort of patients with different types of infantile epilepsy.

[Severe and uncommon complications of anticholinesterase intoxication in children].

Background: The Northern region of the Negev desert is an endemic area of organophosphate and carbamate intoxications in Bedouin children. Most victims are intoxicated by drinking the poisonous material kept by the parents in soft drink bottles. Signs and symptoms of intoxication are commonly known and generally include various effects on the central nervous system, usually a decreased level of consciousness in children, cholinergic muscarinic (sweating, rhinorrhea, miosis, vomiting) and nicotinic (weakness) effects.

Effect of single dose methylphenidate on walking and postural stability under single- and dual-task conditions in older adults--a double-blind randomized control trial.

Background: Methylphenidate (MPH) action may improve executive function and motor function. Effects of MPH on balance function in older adults were investigated.

Methods: A randomized controlled double-blind study examined the effects of a single dose of MPH on gait and postural stability in 30 healthy older adults (mean age = 74.