-
Journal of Biosciences 2020Ankyrins are ubiquitously expressed proteins that play a critical role in the integrity of cytoskeleton and cellular signalling. Their presence in metazoans and... (Review)
Review
Ankyrins are ubiquitously expressed proteins that play a critical role in the integrity of cytoskeleton and cellular signalling. Their presence in metazoans and evolutionary conserved protein primary sequence indicates their functional significance. Tissue-specific isoforms and an array of transcript variants make this protein one of the indispensable cellular components. Membrane-binding domains consist of ankyrin repeats that bind with several functional membrane proteins that enable maintaining cellular integrity. Cytosolic ankyrins help in cellular signal transduction. Linkage studies and recent genome-wide association studies uncovered the pathogenic roles of ankyrins (ankyrin-R, ankyrin-B and ankyrin-G) in several diseases, such as hereditary spherocytosis, long QT syndrome, intellectual disability, and CRASH syndrome, among several others. Identification of in celiac disease may potentially explain the link between neuronal health and immunity. It is thus warranted to investigate the role of neuronal factors in immune diseases and vice versa. In this review, we briefly discussed the contribution of ankyrin genes to human diseases.
Topics: Ankyrins; Celiac Disease; Genetic Diseases, X-Linked; Genome-Wide Association Study; Humans; Intellectual Disability; Long QT Syndrome; Signal Transduction; Spastic Paraplegia, Hereditary; Spherocytosis, Hereditary
PubMed: 33410423
DOI: No ID Found -
The Journal of Gene Medicine Jan 2024Intellectual disability (ID) can be associated with different syndromes such as Rubinstein-Taybi syndrome (RSTS) and can also be related to conditions such as metabolic...
BACKGROUND
Intellectual disability (ID) can be associated with different syndromes such as Rubinstein-Taybi syndrome (RSTS) and can also be related to conditions such as metabolic encephalomyopathic crises, recurrent,with rhabdomyolysis, cardiac arrhythmias and neurodegeneration. Rare congenital RSTS1 (OMIM 180849) is characterized by mental and growth retardation, significant and duplicated distal phalanges of thumbs and halluces, facial dysmorphisms, and an elevated risk of malignancies. Microdeletions and point mutations in the CREB-binding protein (CREBBP) gene, located at 16p13.3, have been reported to cause RSTS. By contrast, TANGO2-related metabolic encephalopathy and arrhythmia (TRMEA) is a rare metabolic condition that causes repeated metabolic crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias and encephalopathy with cognitive decline. Clinicians need more clinical and genetic evidence to detect and comprehend the phenotypic spectrum of this disorder.
METHODS
Exome sequencing was used to identify the disease-causing variants in two affected families A and B from District Kohat and District Karak, Khyber Pakhtunkhwa. Affected individuals from both families presented symptoms of ID, developmental delay and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing.
RESULTS
In the present study, two families (A and B) exhibiting various forms of IDs were enrolled. In Family A, exome sequencing revealed a novel missense variant (NM 004380.3: c.4571A>G; NP_004371.2: p.Lys1524Arg) in the CREBBP gene, whereas, in Family B, a splice site variant (NM 152906.7: c.605 + 1G>A) in the TANGO2 gene was identified. Sanger sequencing of both variants confirmed their segregation with ID in both families. The in silico tools verified the aberrant changes in the CREBBP protein structure. Wild-type and mutant CREBBP protein structures were superimposed and conformational changes were observed likely altering the protein function.
CONCLUSIONS
RSTS and TRMEA are exceedingly rare disorders for which specific clinical characteristics have been clearly established, but more investigations are underway and required. Multicenter studies are needed to increase our understanding of the clinical phenotypes, mainly showing the genotype-phenotype associations.
Topics: Humans; CREB-Binding Protein; Intellectual Disability; Mutation; Mutation, Missense; Phenotype; Rhabdomyolysis; Rubinstein-Taybi Syndrome
PubMed: 37721116
DOI: 10.1002/jgm.3591 -
Psicothema Aug 2019The field of intellectual and developmental disabilities (IDD) is currently experiencing a significant transformation that encompasses an integrated approach, especially... (Review)
Review
BACKGROUND
The field of intellectual and developmental disabilities (IDD) is currently experiencing a significant transformation that encompasses an integrated approach, especially regarding shared aspects such as a focus on the human and legal rights, the eligibility for services and supports, and an emphasis on individualized supports provided within inclusive community-based environments. Accompanying this transformation is the increased need of precision in both the operational definitions of IDD-related constructs, and the terminology used to describe the respective construct.
METHOD
the specialized literature was revised, and previous works on the subject by the authors were updated.
RESULTS
This article provides psychologists with the current definition of intellectual disability, operational definitions of intellectual disability and developmental disabilities constructs and associated terminology, and the parameters of an integrated approach to disability.
CONCLUSIONS
Implications for psychologists who are involved in diagnosis, classification, and planning supports for persons with intellectual or developmental disability are discussed.
Topics: Adaptation, Psychological; Civil Rights; Cognition; Delivery of Health Care, Integrated; Developmental Disabilities; Disabled Persons; Humans; Intellectual Disability; Intelligence; Interpersonal Relations; Learning Disabilities; Psychological Theory; Psychology; Risk Factors; Social Skills; Social Support; Terminology as Topic
PubMed: 31292035
DOI: 10.7334/psicothema2019.119 -
Computers in Biology and Medicine Aug 2022At present, the assessment of mental retardation is mainly based on clinical interview, which requires the participation of experienced psychiatrist and is laborious....
At present, the assessment of mental retardation is mainly based on clinical interview, which requires the participation of experienced psychiatrist and is laborious. Studies have shown that there are correlations between mental retardation and abnormal behaviors (such as, hyperkinetic, tics, stereotypes, etc.). On the basis of this fact, a two stream Non-Local CNN-LSTM network has been proposed to learn the features of upper body behavior and facial expression of patients, thus, to achieve the preliminary screening of mental retardation. Specifically, RGB and optical flow are extracted separately from interview videos, and a two stream network based on contribution mechanism is designed to effectively fuse the information of two kinds of images, which may update the network in a new approach of alternating iteration training to find the optimal model. Besides, by introducing non-local mechanism and adopting it to the network, the global feature sensing can be established more effectively to reduce the background interference for video clip in a short time zone. Experiments on clinical video dataset show that the performance of proposed model is better than other prevalent deep learning methods of behavioral feature learning, the accuracy reaches 89.15% in basic experiment, and is further improved to 89.52% in the supplementary experiment. Furthermore, the experimental results show that this method still has a lot of room for improvement. In general, our work indicates that the proposed model has potential value for the clinical diagnosis and screening of mental retardation.
Topics: Humans; Intellectual Disability; Neural Networks, Computer
PubMed: 35809411
DOI: 10.1016/j.compbiomed.2022.105803 -
Psychiatric Services (Washington, D.C.) Mar 2022Individuals with intellectual and developmental disabilities (IDD) are at high risk of co-occurring mental health conditions, including major depressive disorder,...
Individuals with intellectual and developmental disabilities (IDD) are at high risk of co-occurring mental health conditions, including major depressive disorder, bipolar disorder, psychotic disorders, anxiety disorders, impulse control disorders, and others. Because of symptoms associated with these illnesses and with the disabilities themselves, these individuals are often served in a mental health service system framework. In this second of two articles on care for persons with IDD in the mental health system, the authors focus on policy and systems considerations to assist practitioners and administrators to provide high-quality mental health services for these individuals by recognizing existing infrastructures of support. The authors describe historical factors, including legislation and case law, that have led to greater inclusion of persons with IDD in mainstream settings; systemic barriers to integrating services for persons with IDD and Medicaid waivers and provisions of the Affordable Care Act designed to overcome such barriers; and considerations for treating persons with IDD in various settings, such as emergency departments and forensic settings. They propose approaches to developing the workforce, such as by training direct service professionals and utilizing the services of board-certified behavioral analysts. A robust continuum of care and service delivery system that is increasingly sophisticated in working with persons with IDD, with and without co-occurring mental illness, is critical to maximize the autonomy and community inclusion of these individuals.
Topics: Child; Depressive Disorder, Major; Developmental Disabilities; Humans; Intellectual Disability; Mental Health; Patient Protection and Affordable Care Act; Policy; United States
PubMed: 34346727
DOI: 10.1176/appi.ps.201900505 -
Journal of Nippon Medical School =... May 2022Determining when caregivers should take their children to a hospital is crucial in ensuring the health and safety of children. Because children cannot make these...
BACKGROUND
Determining when caregivers should take their children to a hospital is crucial in ensuring the health and safety of children. Because children cannot make these decisions on their own, caregivers bear the core responsibility for the wellness of their children. The aim of this study was to determine how disease, disability, and child behavior affect when and how often caregivers take their children to a hospital.
METHODS
A structured anonymous online survey was circulated to pediatricians in Japan. Pediatricians were queried about the characteristics of their patients, including reactivity to pain, expression of pain, behavior at the hospital, and the timing of presentation. Patients were school-aged children and included those with autism spectrum disorder, attention-deficit hyperactivity disorder, Down syndrome, mental retardation, epilepsy, premature birth, and allergies.
RESULTS
Sixty-eight of 80 pediatricians responded to the survey (85% response rate). The results indicated that caregivers of children with autism spectrum disorder, attention-deficit hyperactivity disorder, and mental retardation took them to the hospital later than was optimal. Conversely, children born prematurely and those with allergies were taken to hospitals even when symptoms were mild.
CONCLUSIONS
Caregivers make decisions on when to present to hospital on the basis of their child's expression of pain and behavior. Guidelines should be developed to assist caregivers in determining when to present for treatment at a hospital.
Topics: Autism Spectrum Disorder; Child; Hospitals; Humans; Hypersensitivity; Intellectual Disability; Pain; Pediatricians
PubMed: 34526461
DOI: 10.1272/jnms.JNMS.2022_89-214 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Feb 2023Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global...
Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.
Topics: Humans; Male; Female; Child; Infant; Intellectual Disability; Mental Retardation, X-Linked; Obesity; Hypogonadism
PubMed: 36999477
DOI: 10.11817/j.issn.1672-7347.2023.220414 -
Molecular Psychiatry Aug 2020The Fragile X Mental Retardation Protein (FMRP) is an RNA-binding protein essential to the regulation of local translation at synapses. In the mammalian brain, synapses... (Review)
Review
The Fragile X Mental Retardation Protein (FMRP) is an RNA-binding protein essential to the regulation of local translation at synapses. In the mammalian brain, synapses are constantly formed and eliminated throughout development to achieve functional neuronal networks. At the molecular level, thousands of proteins cooperate to accomplish efficient neuronal communication. Therefore, synaptic protein levels and their functional interactions need to be tightly regulated. FMRP generally acts as a translational repressor of its mRNA targets. FMRP is the target of several post-translational modifications (PTMs) that dynamically regulate its function. Here we provide an overview of the PTMs controlling the FMRP function and discuss how their spatiotemporal interplay contributes to the physiological regulation of FMRP. Importantly, FMRP loss-of-function leads to Fragile X syndrome (FXS), a rare genetic developmental condition causing a range of neurological alterations including intellectual disability (ID), learning and memory impairments, autistic-like features and seizures. Here, we also explore the possibility that recently reported missense mutations in the FMR1 gene disrupt the PTM homoeostasis of FMRP, thus participating in the aetiology of FXS. This suggests that the pharmacological targeting of PTMs may be a promising strategy to develop innovative therapies for patients carrying such missense mutations.
Topics: Animals; Fragile X Mental Retardation Protein; Fragile X Syndrome; Humans; Neurons; Protein Processing, Post-Translational; Synapses
PubMed: 31822816
DOI: 10.1038/s41380-019-0629-4 -
Human Genetics Dec 2021ATR-X, an acronym for alpha thalassemia and mental retardation X-linked, syndrome is a congenital condition predominantly affecting males, characterized by mild to...
ATR-X, an acronym for alpha thalassemia and mental retardation X-linked, syndrome is a congenital condition predominantly affecting males, characterized by mild to severe intellectual disability, facial, skeletal, urogenital, and hematopoietic anomalies. Less common are heart defects, eye anomalies, renal abnormalities, and gastrointestinal dysfunction. ATR-X syndrome is caused by germline variants in the ATRX gene. Until recently, the diagnosis of the ATR-X syndrome had been guided by the classical clinical manifestations and confirmed by molecular techniques. However, our new systematic analysis shows that the only clinical sign shared by all affected individuals is intellectual disability, with the other manifestations varying even within the same family. More than 190 different germline ATRX mutations in some 200 patients have been analyzed. With improved and more frequent analysis by molecular technologies, more subtle deletions and insertions have been detected recently. Moreover, emerging technologies reveal non-classic phenotypes of ATR-X syndrome as well as the description of a new clinical feature, the development of osteosarcoma which suggests an increased cancer risk in ATR-X syndrome. This review will focus on the different types of inherited ATRX mutations and their relation to clinical features in the ATR-X syndrome. We will provide an update of the frequency of clinical manifestations, the affected organs, and the genotype-phenotype correlations. Finally, we propose a shift in the diagnosis of ATR-X patients, from a clinical diagnosis to a molecular-based approach. This may assist clinicians in patient management, risk assessment and genetic counseling.
Topics: Animals; Humans; Intellectual Disability; Mental Retardation, X-Linked; Molecular Diagnostic Techniques; Mutation; alpha-Thalassemia
PubMed: 34524523
DOI: 10.1007/s00439-021-02361-5 -
Journal of Intellectual Disabilities :... Sep 2022Fragile X syndrome (FXS) has a classic phenotype, however its expression can be variable among full mutation males. This is secondary to variable methylation mosaicisms...
Fragile X syndrome (FXS) has a classic phenotype, however its expression can be variable among full mutation males. This is secondary to variable methylation mosaicisms and the number of CGG triplet repeats in the non-coding region of the Fragile X Mental Retardation 1 () gene, producing a variable expression of the Fragile X Mental Retardation Protein (FMRP). Here we report a family with several individuals affected by FXS: a boy with a hypermethylated mutation and a classic phenotype; a man with an gene mosaicism in the range of premutation (PM) and full mutation (FM), who has a mild phenotype due to which FXS was initially disregarded; and the cases of four women with a FM and mosaicism. This report highlights the importance of DNA molecular testing for the diagnosis of FXS in patients with developmental delay, intellectual disability and/or autism due to the variable phenotype that occurs in individuals with mosaicisms.
Topics: Female; Fragile X Mental Retardation Protein; Fragile X Syndrome; Humans; Intellectual Disability; Male; Mosaicism; Mutation; Phenotype
PubMed: 33998336
DOI: 10.1177/1744629521995346