Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An offspring of a class F diabetic primigravida with marginal control during the first 8 weeks of the gestation had a level II sonogram at 23 weeks. It showed polyhydramnios and "hydrocephaly." Macrosomia, right hydroureter, megacystis and premature birth corroborated the diagnostic impression of diabetic embryopathy. At age 3 years, the child functions within the moderate range of mental retardation. Angiography, choanogram, CT and MRI scans showed unique CNS abnormalities that appeared secondary to a hamartomatous growth within the left cerebral hemisphere. Such anomaly, most likely a part of the phenotype of the diabetic embryopathy, implies a growth disturbance secondary to dysregulated paracrine growth factors (somatomedins, nerve growth factor, panregulin and/or their receptors in this case). It also indicates a possibility of interaction between two dysregulated major growth mechanisms; the endocrine in the mother considered responsible for the overall phenotype of the diabetic embryopathy/fetopathy and the paracrine fine tuning mechanism in the embryo incriminated by the hamartomatous over/undergrowth.
 ...
PMID:Unique brain anomalies in an infant of a diabetic mother. 202 82

West syndrome is a strictly age-limited encephalopathy of early infancy with unknown pathogenesis. It is often progressive, leading to mental retardation. Neurotrophic factors are important for the regulation of neuronal survival and differentiation, and their expression is influenced by hormones. Levels of beta-nerve growth factor in the cerebrospinal fluid were examined by two-site enzyme-linked immunosorbent assay method. Human antigen was used as a standard. We present data on largely normal levels of nerve growth factor in the cerebrospinal fluid of infants with cryptogenic etiology, but low or negligible levels in infants with symptomatic etiology, and very high levels in infants with symptomatic postinfectious etiology. Treatment with ACTH led to a greater increase in patients with a good response than in those with a poor response. Low nerve growth factor in patients with symptomatic infantile spasms possibly reflects massive neuronal death. The regression seen in these infants and their poor response to ACTH therapy may be due in part to lack of growth factors supporting neuron survival. This study, previously only demonstrated in animal models, is the first to depict nerve growth factor gene activity in humans as modulated by steroids.
 ...
PMID:West syndrome: cerebrospinal fluid nerve growth factor and effect of ACTH. 939 Jun 98

Williams syndrome (SW) is a rare (2-5/100,000) genetic human disorder characterised by a typical facies and mental retardation with a deficit in the visuo-spatial cognitive function and a relative preservation of linguistic abilities. This syndrome also includes morphological anomalies and metabolic-functional impairments, likely deficits in the pattern of brain ontogenesis. Neuropsychological and somatic features of the SW individuals are illustrated, and the correspondent genetic bases, recently identified, are presented. The possible role of NGF (nerve growth factor), a particular neurotrophin involved in the development of brain cholinergic system and the associated behavioural functions, in the aetiology of the typical mental retardation of SW patients, is critically discussed. Prospect of researches, including the identification of potential neurobiological markers and the definition of appropriate cognitive profiles of the SW, in order to precociously diagnose this syndrome, and a more thorough investigation of factors affecting phenotypic expression of this genetically determined pathological condition, are reviewed.
 ...
PMID:[Williams syndrome: a window to the development of cognitive and neural processes]. 947 Feb 50

Indices of both platelet serotoninergic system and the system of nerve growth factor (NGF) were examined in children with neurofibromatosis (15 patients), polygenic oligophrenia (24 patients) and Rett's syndrome (14 ones). There was an increase of both the level of blood serum autoantibodies (aAB) to NGF and the value of specific binding of 3H-imipramine (Bmax) in platelets of patients with oligophrenia. For this group of patients a significant negative correlation exists between the rate of platelet uptake of serotonin (Vmax value) and the degree of mental retardation (r = -0.425, p < 0.03). Decrease of both Vmax and activity of platelet NGF receptors was revealed in patients with neurofibromatosis. In such patients there was positive correlation between sensitivity of platelet NGF receptors to NGF (during their stimulation by test dose of purified NGF) and the degree of mental retardation (r = 0.697, p < 0.04). In patients with Rett's syndrome a significant increase of activity of platelet NGF receptors to NGF was observed. The conclusion was made on the existence of some general mechanism of intellectual defect development. Autoimmune processes considered to be such mechanism.
 ...
PMID:[The indices of the thrombocyte serotonin system and of the nerve growth factor system in children with hereditary disorders of neuropsychic development]. 957 27

Lesch-Nyhan syndrome is a hereditary disorder of purine metabolism causing overproduction of uric acid and neurological problems including spasticity, choreoathetosis, mental retardation, and compulsive self-mutilation. The syndrome is caused by a defect in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT), which converts guanine and hypoxanthine to the nucleotides GMP and IMP. There is evidence that the neurological problems are due to an adverse effect of the HPRT deficiency on the survival and/or development of dopaminergic neurons, specifically. Here we report that HPRT-deficient PC12 mutants that have a normal or near normal dopamine content (55-97% of that of wild-type cells) fail to undergo neuronal differentiation induced by nerve growth factor (NGF) when the de novo pathway of purine synthesis is partially inhibited. However, nerve growth factor-induced differentiation is near normal under these conditions in PC12 HPRT-deficient mutants containing much lower dopamine levels (<8% of that of wild type cells), indicating a neurotoxic effect of the endogenous dopamine in the mutants. The degree of inhibition of the de novo pathway of purine synthesis was the same in both classes of HPRT-deficient mutants. Expression of BCl-2 in a PC12 mutant that has a normal dopamine content allowed partial NGF-induced differentiation suggesting that the apoptotic pathway might be involved in the failure of differentiation when the de novo pathway of purine synthesis is partially inhibited.
 ...
PMID:Impaired differentiation of HPRT-deficient dopaminergic neurons: a possible mechanism underlying neuronal dysfunction in Lesch-Nyhan syndrome. 967 Sep 94

Congenital insensitivity to pain with anhidrosis (CIPA) is characterized by recurrent episodes of unexplained fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. Human TRKA encodes a high-affinity tyrosine kinase receptor for nerve growth factor (NGF), a member of the neurotrophin family that induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. We have recently demonstrated that TRKA is responsible for CIPA by identifying three mutations in a region encoding the intracellular tyrosine kinase domain of TRKA in one Ecuadorian and three Japanese families. We have developed a comprehensive strategy to screen for TRKA mutations, on the basis of the gene's structure and organization. Here we report 11 novel mutations, in seven affected families. These are six missense mutations, two frameshift mutations, one nonsense mutation, and two splice-site mutations. Mendelian inheritance of the mutations is confirmed in six families for which parent samples are available. Two mutations are linked, on the same chromosome, to Arg85Ser and to His598Tyr;Gly607Val, hence, they probably represent double and triple mutations. The mutations are distributed in an extracellular domain, involved in NGF binding, as well as the intracellular signal-transduction domain. These data suggest that TRKA defects cause CIPA in various ethnic groups.
 ...
PMID:Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor. 1033 Mar 44

Williams syndrome (WS) is a rare (2-5/100,000) genetic human disorder characterised by a typical facies and mental retardation with a deficit in the visuospatial cognitive function and a relative preservation of linguistic abilities in general, and spoken language in particular. This syndrome also includes morphological anomalies, metabolic functional impairments, and likely deficits in the pattern of brain ontogenesis. The genetic basis of WS, recently identified, are presented. A cognitive profile of the WS individuals is defined and compared to Down syndrome (DS) and autism cognitive profiles. Neuroanatomical features of WS, including a reduction in brain volume, preservation of cerebellum and frontal lobes, and a reduction of posterior cortical systems, are described. The possible role of NGF (nerve growth factor)--a neurotrophin involved in the development of brain cholinergic systems and the associated behavioural functions--in the aetiology of the typical mental retardation of WS patients, is critically discussed. Future research avenues, including the identification of potential neurobiological markers in order to precociously diagnose this syndrome, are reviewed.
 ...
PMID:[Williams syndrome]. 1064 54

In a previous paper published in this journal, we reported two cases of "Congenital Sensory Neuropathy with Anhidrosis" with reference to the orthopedic complications (Theodorou et al., 1985). We now present a new typical case, under the currently used term: "Congenital Insensitivity to Pain with Anhidrosis" (CIPA) and a brief review of the literature on the incidence, etiology and problems arising in various systems. CIPA is an autosomal recessive form of sensory neuropathy manifesting with typical clinical features. Universal insensitivity to pain, anhidrosis or hypohidrosis, bouts of hyperpyrexia from very young age, self inflicted injuries, defective or absent lacrimation and mental retardation are specific diagnostic findings. Orthopedic, maxillofacial, dermatological and ophthalmologic complications are common. Counseling of the family and school personnel for the prevention of injuries is necessary. Early diagnosis is very important for the prevention and treatment of various complications. The etiology and pathogenesis of the condition is still unclear. The recent detection of a new gene, which encodes a receptor tyrosine kinase for nerve growth factor and lately of a specific point mutation associated with the gene inactivation11, may open new ways for the study and management of this disabling condition.
 ...
PMID:Congenital insensitivity to pain with anhidrosis. Report of a case and review of the literature. 1084 74

The human TRKA gene encodes a high-affinity tyrosine kinase receptor for nerve growth factor. Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive genetic disorder reported from various countries and characterized by anhidrosis (inability to sweat), the absence of reaction to noxious stimuli, and mental retardation. We have found that TRKA is the gene responsible for CIPA. We have studied TRKA in 46 CIPA chromosomes derived from 23 unrelated Japanese CIPA families. including three that have been previously reported, and identified 11 novel mutations. Four (L93P, G516R, R648 C, and D668Y) are missense mutations that result in amino acid substitutions at positions conserved in the TRK family, including TRKA, TRKB, and TRKC. Three (S131 fs, L579 fs, and D770 fs) are frameshift mutations. Three (E164X, Y359X, and R596X) are nonsense mutations. The other is an intronic branch-site (IVS7-33T-->A) mutation, causing aberrant splicing in vitro. We also report the characterization of eight intragenic polymorphic sites, including a variable dinucleotide repeat and seven single nucleotide polymorphisms, and describe the haplotypic associations of alleles at these sites in 106 normal chromosomes and 46 CIPA chromosomes. More than 50% of CIPA chromosomes share the frameshift mutation (R548 fs) that we described earlier. This mutation apparently shows linkage disequilibrium with a rare haplotype in normal chromosomes, strongly suggesting that it is a common founder mutation. These findings represent the first extensive analysis of CIPA mutations and associated intragenic polymorphisms; they should facilitate the detection of CIPA mutations and aid in the diagnosis and genetic counseling of this painless but severe genetic disorder with devastating complications.
 ...
PMID:Mutation and polymorphism analysis of the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor in congenital insensitivity to pain with anhidrosis (CIPA) families. 1098 91

There has been little exploration of major biologic regulators of cerebral development in autism. In archived neonatal blood of children with autistic spectrum disorders (n = 69), mental retardation without autism (n = 60), or cerebral palsy (CP, n = 63) and of control children (n = 54), we used recycling immunoaffinity chromatography to measure the neuropeptides substance P (SP), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), and the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4/5 (NT4/5). Neonatal concentrations of VIP, CGRP, BDNF, and NT4/5 were higher (ANOVA, all p values < 0.0001 by Scheffe test for pairwise differences) in children in the autistic spectrum and in those with mental retardation without autism than in control children. In 99% of children with autism and 97% with mental retardation, levels of at least one of these substances exceeded those of all control children. Concentrations were similar in subgroups of the autistic spectrum (core syndrome with or without mental retardation, other autistic spectrum disorders with or without mental retardation) and in the presence or absence of a history of regression. Among children with mental retardation, concentrations did not differ by severity or known cause (n = 11, including 4 with Down syndrome). Concentrations of measured substances were similar in children with CP as compared with control subjects. SP, PACAP, NGF, and NT3 were not different by diagnostic group. No measured analyte distinguished children with autism from children with mental retardation alone. In autism and in a heterogeneous group of disorders of cognitive function, overexpression of certain neuropeptides and neurotrophins was observed in peripheral blood drawn in the first days of life.
 ...
PMID:Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. 1135 50


1 2 3 Next >>