Adi Aran

Shaare Zedek Medical Center | szmc · Department of Pediatrics

Mutations in over 100 genes are implicated in autism spectrum disorder (ASD). DNA mutations and epigenomic modifications also contribute to ASD. Transcriptomics analysis of blood samples may offer clues for pathways dysregulated in ASD. To expand and validate published findings of RNA-sequencing (RNA-seq) studies, we performed RNA-seq of whole bloo...

Date Presented Accepted for AOTA INSPIRE 2021 but unable to be presented due to online event limitations. It is important for humans to efficiently detect changes occurring around them for social interaction, learning, and movement, as well as survival and protection (Kessler, 2006). Adolescents with attention deficit hyperactivity disorder demonst...

Objective To determine the yield of genetic diagnoses using chromosomal microarray (CMA) and trio whole exome sequencing (WES), separately and combined, among patients with cryptogenic cerebral palsy (CP). Methods Trio WES of patients with prior CMA analysis for cryptogenic CP, defined as disabling, non-progressive motor symptoms beginning before...

Background Social interaction at its core entails allocating attention to relevant stimuli. As such, the perception of change requires attention, but studies have suggested that the social impairment in people with autism spectrum disorder (ASD) occurs at the attentual level of "on-line" social cognition. Method Forty-four young adults—22 with aut...

Background Endocannabinoid dysfunction in animal models of autism spectrum disorder (ASD) and accumulating, albeit anecdotal, evidence for efficacy in humans motivated this placebo-controlled double-blind comparison of two oral cannabinoid solutions in 150 participants (age 5–21 years) with ASD. Methods We tested (1) BOL-DP-O-01-W, a whole-plant c...

Deficiency of the endoplasmic reticulum transmembrane protein ARV1 leads to epileptic encephalopathy in humans and in mice. ARV1 is highly conserved, but its function in human cells is unknown. Studies of yeast arv1 null mutants indicate that it is involved in a number of biochemical processes including the synthesis of sphingolipids and glycosylph...

Background The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emergi...

Aim To investigate the impact of auditory stimulation on motor function in children with cerebral palsy (CP) and disabling hypertonia. Method 9 matched pairs (age: 7y5m, SD 4y1m; 13 boys; gross-motor-functional-classification-scale: median 4; manual-ability-classification-system: median 4) were randomized to receive either auditory stimulation emb...

Adverse effects. Bowel and bladder control (5-point scale), sleep, drooling and head control (4-point scale) and constipation (3-point scale) at baseline and after 5 months. (DOCX)

Raw data. Data of all participants before and after intervention. (PDF)

Gross motor skills before and after treatment. Three children in the treatment group who gained motor skills during the study. The motor skills shown are Sit to Stand, Standing and Walking. The videos were filmed before treatment and after 5 months. (MP4)

Anecdotal evidence of successful cannabis treatment in autism spectrum disorder (ASD) are accumulating but clinical studies are lacking. This retrospective study assessed tolerability and efficacy of cannabidiol-rich cannabis, in 60 children with ASD and severe behavioral problems (age = 11.8 ± 3.5, range 5.0–17.5; 77% low functioning; 83% boys). E...

Type 1 narcolepsy (T1N) is a neurological condition, in which the death of hypocretin-producing neurons in the lateral hypothalamus leads to excessive daytime sleepiness and symptoms of abnormal Rapid Eye Movement (REM) sleep. Known triggers for narcolepsy are influenza-A infection and associated immunization during the 2009 H1N1 influenza pandemic...

Objective To identify the genetic basis of a childhood-onset syndrome of variable severity characterised by progressive spinocerebellar ataxia, mental retardation, psychotic episodes and cerebellar atrophy. Methods Identification of the underlying mutations by whole exome and whole genome sequencing. Consequences were examined in patients’ cells a...

Objective: This retrospective study assessed safety, tolerability and efficacy of cannabidiol (CBD) based medical cannabis, as an adjuvant therapy, for refractory behavioral problems in children with ASD. Background: Anecdotal evidence of successful cannabis treatment in children with autism spectrum disorder (ASD) are accumulating but formal stud...

Visual attention of adolescents with autism spectrum disorder (ASD) was assessed using a change blindness paradigm. Twenty-five adolescents with ASD aged 12–18 years and 25 matched typically developing (TD) adolescents viewed 36 pairs of digitized real-world images. Each pair of images was displayed in a ‘flicker paradigm’ whereby a particular item...

Adults with attention deficit/hyperactivity disorder (ADHD) are prone to suboptimal decision making and risk taking. The aim of this study was to test performance on a theoretically-based probabilistic decision making task in well-characterized adults with and without ADHD, and examine the relation between experimental risk taking and history of re...

Objective: ADHD in adolescents and low level of parental monitoring have been associated with increased risk-taking behavior. The present study examined whether parental knowledge of the child's whereabouts mediates the correlations between adolescent ADHD symptoms and risk-taking behavior. Method: Ninety-two adolescents and their parents comple...

Background: Rhabdomyolysis is a clinical emergency that may cause acute kidney injury (AKI). It can be acquired or due to monogenic mutations. Around 60 different rare monogenic forms of rhabdomyolysis have been reported to date. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to nonspecific presentation,...

Objective To assess the potential connection between PCDH12 and brain calcifications in a patient carrying a homozygous nonsense variant in PCDH12 and in adult patients with brain calcifications. Methods We performed a CT scan in 1 child with a homozygous PCDH12 nonsense variant. We screened DNA samples from 53 patients with primary familial brain...

Introduction: Any medical treatment, whether it be medication, behavioral therapy or medical procedure, can affect the patient in a very complex way. Each of these forms of medical treatment have both psychobiological and physiological effects on the patient, with interactions between those levels. When considering the specific efficacy of a new t...

Objective: To identify the genetic basis of a recessive congenital neurologic syndrome characterized by severe hypotonia, arthrogryposis, and respiratory failure. Methods: Identification of the responsible gene by exome sequencing and assessment of the effect of the mutation on protein stability in transfected rat neuronal-like PC12(A123.7) cell...

Introduction: Imprinted genes are genes whose expression is dependent on parental origin, and are transcribed only from one specific parental allele (monoallelically expressed). The differences in expression are regulated by differentially methylated regions (DMRs) or imprinting control regions (ICRs), which acquire their methylation pattern during...

Introduction A previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic ventilatory response (HCVR) in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in gene...

this table shows the influence of SNPs in the PHOX2B, GPR4 and TASK2/KCNK5 genes on HVR and HCVR using a tagSNP approach including tagging SNPs within 5kb up and downstream of the genes. (XLSX)

Raw data used in the analysis. (XLS)

Background: Legg-Calve-Perthes disease (LCPD) is an idiopathic hip osteonecrosis prevalent in children < age 15 years. The etiology remains incompletely understood, partly because of multiple potential environmental risk factors and partly because of lack of genetic markers. It has been hypothesized that hyperactivity may induce mechanical stress a...

Background: Legg-Calvé-Perthes disease (LCPD) is an idiopathic hip osteonecrosis prevalent in children < age 15 years. The etiology remains incompletely understood, partly because of multiple potential environmental risk factors and partly because of lack of genetic markers. It has been hypothesized that hyperactivity may induce mechanical stress...

Introduction: Imprinted genes are genes whose expression is dependent on parental origin, and are transcribed only from one specific parental allele (monoallelically expressed). The differences in expression are regulated by differentially methylated regions (DMRs) or imprinting control regions (ICRs), which acquire their methylation pattern during...

Mutation in a growing spectrum of genes is known to either cause or contribute to primary or secondary microcephaly. In primary microcephaly the genetic determinants frequently involve mutations that contribute to or modulate the microtubule cytoskeleton by causing perturbations of neuronal proliferation and migration. Here we describe four patient...

Objective: To identify the genetic basis of a recessive syndrome characterized by prenatal hyperechogenic brain foci, congenital microcephaly, hypothalamic midbrain dysplasia, epilepsy, and profound global developmental disability. Methods: Identification of the responsible gene by whole exome sequencing and homozygosity mapping. Results: Ten...

Background: Despite a gradual reduction in the workload during residency, 24-hour calls are still an integral part of most training programs. While sleep deprivation increases the risk propensity, the impact on medical risk taking has not been studied. Objective: This study aimed to assess the clinical decision making and psychomotor performance...

To determine the prevalence and characteristics of copy number variations (CNVs) in children with cerebral palsy (CP) of unknown etiology, comprising approximately 20% of the CP population. Fifty-two participants (age 10.5 ± 7.8 years; Gross Motor Function Classification System scale 2.8 ± 1.3) with nonprogressive pyramidal and/or extrapyramidal si...

Hypocretin (orexin) is a unique neuropeptide involved in the consolidation of wakefulness and sleep. Although hypocretin-1 levels in the cerebrospinal fluid (CSF) are stable after infancy, how levels change in preterm and term human infants is unknown. Hypocretin-1 levels were measured in CSF samples, obtained from 284 preterm (25-37 gestational we...

The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression in peripheral white blood cells of 50 narcolepsy versus 47...

Polymorphisms in the TCRA and P2RY11, two immune related genes, are associated with narcolepsy in Caucasians and Asians. In contrast, CPT1B/CHKB polymorphisms have only been shown to be associated with narcolepsy in Japanese, with replication in a small group of Koreans. Our aim was to study whether these polymorphisms are associated with narcoleps...

Streptococcal infections are known to trigger autoimmune disorders, affecting millions worldwide. Recently, we found an association between post-streptococcal autoantibodies against Protein Disulphide Isomerase (PDI), an enzyme involved in insulin degradation and insulin resistance. This led us to evaluate associations between post-streptococcal an...

Accidental injuries are a leading cause of paediatric morbidity and mortality. We hypothesized that attention deficit hyperactivity disorder (ADHD), a common childhood disorder characterized by behaviours such as hyperactivity and impulsivity, is a risk factor for accidental injuries. Previous retrospective studies suggested that children with ADHD...

To retrospectively describe childhood presentations of primary hypersomnia with an emphasis on narcolepsy-cataplexy in a Chinese population. A total of 417 children (< 18 years old) successively presenting with complaints of hypersomnia without anatomic cause or sleep apnea risk were evaluated using the Stanford Sleep Inventory, human leukocyte ant...

to report on symptoms and therapies used in childhood narcolepsy-cataplexy. retrospective series of 51 children who completed the Stanford Sleep Inventory. HLA-DQB1*0602 typing (all tested, and 100% positive), polysomnography or Multiple Sleep Latency Test (76%), and cerebrospinal fluid hypocretin-1 measurements (26%, all with low levels) were also...

PDI regulates polypeptides structure and function. (A) The reduced amino acid cysteine has a sulphur atom (S), as a thiol group (SH). (B) Disulfide bonds (bridge) are covalent bonds formed between two sulfur atoms across two cysteine residues on a protein or polypeptide, which stabilizes the protein/polypeptide tertiary structure. (C) Oxidized PDI...

Heterogeneity of epitopes in anti-human PDI autoantibodies, and impact on PDI inhibition. (A) Serum samples, positive for anti-bovine PDI, anti-human PDI, or both, were pre-incubated with: 1) PBS; 2) synthetic peptide of the human PDI 11 amino acids determinant -p328-338 (Figure 2C, 100 ng/µl); 3) synthetic peptide of the bovine PDI 11 amino acids...

Characteristics of participants positive for anti-human and bovine PDI antibodies. Data is presented as number (%) of studies or as mean (SEM) for age. #: Adjusted with ASO status; * Caucasians vs. all other ethnic groups. (0.06 MB PDF)

Serum insulin, glucose and HOMA by anti-human PDI status. Data is presented as mean (SEM) or as N-number of studies (%). * Adjusted for age, BMI, gender, smoking and education. HOMA - Homeostatic Model Assessment of insulin resistance. Note: A higher value indicates increased resistance. (0.04 MB PDF)

Post-streptococcal autoimmunity affects millions worldwide, targeting multiple organs including the heart, brain, and kidneys. To explore the post-streptococcal autoimmunity spectrum, we used western blot analyses, to screen 310 sera from healthy subjects with (33%) and without (67%) markers of recent streptococcal infections [anti-Streptolysin O (...

Cerebral Palsy (CP) is a non-progressive disorder of movement and posture caused by a defect or injury to the immature brain and its impact is further exacerbated by disabilities other than the motor impairments, such as epilepsy, learning disabilities, behavioral and emotional problems. Traditionally, the treatment of children with chronic disease...

Narcolepsy-cataplexy has long been thought to have an autoimmune origin. Although susceptibility to narcolepsy, like many autoimmune conditions, is largely genetically determined, environmental factors are involved based on the high discordance rate (approximately 75%) of monozygotic twins. This study evaluated whether Streptococcus pyogenes and He...

In this study we examined interrelations among locus of control (LOC), disease severity, anxiety, and parenting style (PS) in children with cerebral palsy (CP). Thirty children with CP and their 30 healthy siblings completed self-report measures of LOC, anxiety, and perceived PS of the mother. A neurological assessment determined severity of CP. Ch...

To assess the impact of parenting style and disease severity on quality of life (QOL) in children with cerebral palsy (CP). Thirty-nine children with CP, their siblings, and their parents participated in the study. Probands and siblings, ages 6 to 18 years, completed questionnaires on parenting style (accepting, rejecting, controlling, and autonomy...

Transcriptional activation of the hepatic phosphoenolpyruvate carboxykinase (PEPCK) gene at birth is critical since PEPCK appearance initiates hepatic gluconeogenesis. A delayed appearance results in hypoglycemia, while a premature appearance results in neonatal diabetes, both are incompatible with sustaining life. Experiments using transgenic mice...

Characterization and cloning of liver-enriched transcription factors have provided the tools to study the regulation of liver differentiation. Characterization of the temporal and spatial expression of these factors have shown a sequential order of appearance, in coordination with the expression of their target genes, during liver development. Evid...

To study the transcriptional regulation of the liver gluconeogenic phenotype, the underdifferentiated mouse Hepa-1c1c7 (Hepa) hepatoma cell line was used. These cells mimicked the fetal liver by appreciably expressing the alpha-fetoprotein and albumin genes but not the phosphoenolpyruvate carboxykinase (PEPCK) gene. Unlike the fetal liver, however,...

To study the transcriptional regulation of the liver gluconeogenic phenotype, the underdifferentiated mouse Hepa-1c1c7 (Hepa) hepatoma cell line was used. These cells mimicked the fetal liver by appreciably expressing the alpha-fetoprotein and albumin genes but not the phosphoenolpyruvate carboxykinase (PEPCK) gene. Unlike the fetal liver, however,...