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Gaceta Medica de Mexico 2020Fragile X syndrome is the monogenetic condition that produces more cases of autism and intellectual disability. The repetition of CGG triplets (> 200) and their... (Review)
Review
Fragile X syndrome is the monogenetic condition that produces more cases of autism and intellectual disability. The repetition of CGG triplets (> 200) and their methylation entail the silencing of the FMR1 gene. The FMRP protein (product of the FMR1 gene) interacts with ribosomes by controlling the translation of specific messengers, and its loss causes alterations in synaptic connectivity. Screening for fragile X syndrome is performed by polymerase chain reaction. Current recommendation of the American Academy of Pediatrics is to test individuals with intellectual disability, global developmental retardation or with a family history of presence of the mutation or premutation. Hispanic countries such as Colombia, Chile and Spain report high prevalence of fragile X syndrome and have created fragile X national associations or corporations that seek to bring patients closer to available diagnostic and treatment networks.
Topics: Attention Deficit Disorder with Hyperactivity; Autistic Disorder; Checklist; Child, Preschool; Female; Fragile X Mental Retardation Protein; Fragile X Syndrome; Gene Silencing; Genetic Testing; Humans; Intellectual Disability; Male; Mutation; Pedigree; Phenotype; Ribosomes; Sex Factors; Synaptic Transmission
PubMed: 32026885
DOI: 10.24875/GMM.19005275 -
Journal of Mother and Child Mar 2022Joubert syndrome (JS; MIM PS213300) is a rare genetic autosomal recessive disease characterized by cerebellar vermis hypoplasia, a distinctive malformation of the... (Review)
Review
Joubert syndrome (JS; MIM PS213300) is a rare genetic autosomal recessive disease characterized by cerebellar vermis hypoplasia, a distinctive malformation of the cerebellum and the so-called "molar tooth sign." Other characteristic features are hypotonia with lateral ataxia, intellectual disability/mental retardation, oculomotor apraxia, retinal dystrophy, abnormalities in the respiratory system, renal cysts, hepatic fibrosis, and skeletal changes. Such pleiotropic characteristics are typical of many disorders involving primary cilium aberrations, providing a significant overlap between JS and other ciliopathies such as nephronophthisis, Meckel syndrome, and Bardet-Biedl syndrome. This review will describe some characteristics of JS associated with changes in 35 genes, and will also address subtypes of JS, clinical diagnosis, and the future of therapeutic developments.
Topics: Humans; Cerebellum; Abnormalities, Multiple; Eye Abnormalities; Retina; Polycystic Kidney Diseases; Intellectual Disability
PubMed: 36803942
DOI: 10.34763/jmotherandchild.20222601.d-22-00034 -
Italian Journal of Pediatrics Apr 2017Fragile X Syndrome (FXS) is the second cause of intellectual disability after Down syndrome and the most prevalent cause of intellectual disability in males, affecting... (Review)
Review
BACKGROUND
Fragile X Syndrome (FXS) is the second cause of intellectual disability after Down syndrome and the most prevalent cause of intellectual disability in males, affecting 1:5000-7000 men and 1:4000-6000 women. It is caused by an alteration of the FMR1 gene, which maps at the Xq27.3 band: more than 99% of individuals have a CGG expansion (>200 triplets) in the 5' UTR of the gene, and FMR1 mutations and duplication/deletion are responsible for the remaining (<1%) molecular diagnoses of FXS. The aim of this review was to gather the current clinical and molecular knowledge about FXS to provide clinicians with a tool to guide the initial assessment and follow-up of FXS and to offer to laboratory workers and researchers an update about the current diagnostic procedures.
DISCUSSION
FXS is a well-known condition; however, most of the studies thus far have focused on neuropsychiatric features. Unfortunately, some of the available studies have limitations, such as the paucity of patients enrolled or bias due to the collection of the data in a single-country population, which may be not representative of the average global FXS population. In recent years, insight into the adult presentation of the disease has progressively increased. Pharmacological treatment of FXS is essentially symptom based, but the growing understanding of the molecular and biological mechanisms of the disease are paving the way to targeted therapy, which may reverse the effects of FMRP deficiency and be a real cure for the disease itself, not just its symptoms.
CONCLUSIONS
The clinical spectrum of FXS is wide, presenting not only as an isolated intellectual disability but as a multi-systemic condition, involving predominantly the central nervous system but potentially affecting any apparatus. Given the relative high frequency of the condition and its complex clinical management, FXS appears to have an important economic and social burden.
Topics: Disease Progression; Female; Fragile X Mental Retardation Protein; Fragile X Syndrome; Humans; Intellectual Disability; Male; Mutation; Prognosis; Rare Diseases
PubMed: 28420439
DOI: 10.1186/s13052-017-0355-y -
British Medical Journal Dec 1963
Topics: Humans; Intellectual Disability; Names; Terminology as Topic
PubMed: 14066200
DOI: 10.1136/bmj.2.5373.1653-c -
The Journal of Neuroscience : the... Nov 2017Intellectual disability (ID) is a prevailing neurodevelopmental condition associated with impaired cognitive and adaptive behaviors. Many chromatin-modifying enzymes and... (Review)
Review
Intellectual disability (ID) is a prevailing neurodevelopmental condition associated with impaired cognitive and adaptive behaviors. Many chromatin-modifying enzymes and other epigenetic regulators have been genetically associated with ID disorders (IDDs). Here we review how alterations in the function of histone modifiers, chromatin remodelers, and methyl-DNA binding proteins contribute to neurodevelopmental defects and altered brain plasticity. We also discuss how progress in human genetics has led to the generation of mouse models that unveil the molecular etiology of ID, and outline the direction in which this field is moving to identify therapeutic strategies for IDDs. Importantly, because the chromatin regulators linked to IDDs often target common downstream genes and cellular processes, the impact of research in individual syndromes goes well beyond each syndrome and can also contribute to the understanding and therapy of other IDDs. Furthermore, the investigation of these disorders helps us to understand the role of chromatin regulators in brain development, plasticity, and gene expression, thereby answering fundamental questions in neurobiology.
Topics: Epigenesis, Genetic; Epigenomics; Humans; Intellectual Disability
PubMed: 29118205
DOI: 10.1523/JNEUROSCI.1840-17.2017 -
BMJ (Clinical Research Ed.) Jul 1988
Topics: Child; Dose-Response Relationship, Radiation; Female; Humans; Intellectual Disability; Pregnancy; Prenatal Exposure Delayed Effects; Radiation Dosage
PubMed: 3408951
DOI: 10.1136/bmj.297.6642.153 -
Ciencia & Saude Coletiva Jun 2013Mental retardation (MR) is a definition which comprises a series of conditions whose common feature is an intellectual handicap that develops before the age of 18,... (Review)
Review
Mental retardation (MR) is a definition which comprises a series of conditions whose common feature is an intellectual handicap that develops before the age of 18, afflicting 2-3% of the world's population. The classification of MR into different categories is determined by the extent of the handicap instead of its cause, which often remains unrecognized. Sometimes, MR runs in a family, characterizing familial MR, and those cases permit an in-depth look into the genetic causes and consequences of the problem. However, almost no work is available on the prevalence of familial MR among the registered MR cases, possibly because familial MR is a term with no clear definition. The scope of this work is to review the topic and discuss the implications of different genetic and environmental factors, which characterize particular categories of familial cases, suggesting a practical classification of familial MR, which is important for epidemiologic studies and also for counseling in the clinic. Some of the aspects are discussed under the perspective of a newly-developed country like Brazil.
Topics: Humans; Intellectual Disability; Pedigree
PubMed: 23752538
DOI: No ID Found -
Journal of the Royal College of... 1994The past five years have witnessed rapid and apparently relentless progress in the delineation of the genetic basis of disorders associated with mental retardation. Each... (Review)
Review
The past five years have witnessed rapid and apparently relentless progress in the delineation of the genetic basis of disorders associated with mental retardation. Each gene discovery has a new story to tell but inevitably generates further questions. For the clinical geneticist and, perhaps more importantly, for patients and their families, many of these recent discoveries have yielded information which has immediate implications for diagnostic testing, family and population screening and prenatal testing. Many of the ethical issues consequent upon the rapid progress are only now being addressed. This article highlights a number of disorders whose molecular genetic basis has recently been further characterised. Brain development and maintenance of neurological networks provide the unifying theme; the genetic defects are disparate and each of their mechanisms appears to be novel.
Topics: Chromosome Deletion; Fragile X Syndrome; Genes, Tumor Suppressor; Genetic Counseling; Genetic Testing; Humans; Intellectual Disability; Mutation; Myotonic Dystrophy; Pedigree; Tuberous Sclerosis; alpha-Thalassemia
PubMed: 8006863
DOI: No ID Found -
Journal of Physiology, Paris 2014Intellectual disability, commonly known as mental retardation in the International Classification of Disease from World Health Organization, is the term that describes... (Review)
Review
Intellectual disability, commonly known as mental retardation in the International Classification of Disease from World Health Organization, is the term that describes an intellectual and adaptive cognitive disability that begins in early life during the developmental period. Currently the term intellectual disability is the preferred one. Although our understanding of the physiological basis of learning and learning disability is poor, a general idea is that such condition is quite permanent. However, investigations in animal models suggest that learning disability can be functional in nature and as such reversible through pharmacology or appropriate learning paradigms. A fraction of the cases of intellectual disability is caused by point mutations or deletions in genes that encode for proteins of the RAS/MAP kinase signaling pathway known as RASopathies. Here we examined the current understanding of the molecular mechanisms involved in this group of genetic disorders focusing in studies which provide evidence that intellectual disability is potentially treatable and curable. The evidence presented supports the idea that with the appropriate understanding of the molecular mechanisms involved, intellectual disability could be treated pharmacologically and perhaps through specific mechanistic-based teaching strategies.
Topics: Animals; Humans; Intellectual Disability; Mitogen-Activated Protein Kinase Kinases; Models, Biological; Mutation; Signal Transduction; ras Proteins
PubMed: 24859216
DOI: 10.1016/j.jphysparis.2014.05.003 -
British Medical Journal Nov 1963
Topics: Child; Humans; Intellectual Disability; Names; Terminology as Topic
PubMed: 14077805
DOI: 10.1136/bmj.2.5366.1201-b