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

Calcium hopantenate (HOPA-Ca), which is obtained by substituting the beta-alanine of pantothenic acid for gamma-amino butyric acid (GABA), is a therapeutic drug for mental retardation and cerebrovascular dementia. HOPA-Ca is known to produce convulsive seizures in some patients although it is also true that this improves EEG abnormalities and suppresses epileptic seizures. Thus, clinical observations suggest that HOPA-Ca exerts a paradoxical influence on epilepsy. In order to gain further insight into the influence of HOPA-Ca on epilepsy, we examined its effects on the generalized seizure-triggering threshold (GST) of kindled amygdaloid (AM) seizure and on the rate of AM kindling in rats. Male Wistar rats weighing 200-250 g were used. Under pentobarbital anesthesia, a bipolar electrode, made of twisted stainless steel wire 0.2 mm in diameter, was stereotaxically implanted into the left AM. Daily electrical stimulation was given at the intensity of afterdischarge threshold (ADT). Electrical stimulation was continued until at least five consecutive generalized convulsions were evoked. Subsequently, the stimulus intensity was daily lowered by 20-microA steps and the last stimulus intensity for evoking generalized convulsion was designated as the GST. Experiment 1. Influence of HOPA-Ca on the GST; HOPA-Ca was dissolved in saline as a vehicle. Injections of 50, 100, 250, 500 mg/kg HOPA-Ca were given intraperitoneally 60 min before the stimulation at the GST. The GST never changed with vehicle injection. The GST increase was never observed with any amount of HOPA-Ca. However, the GST dropped flowing HOPA-Ca infection independent of its amount. The GST reduction was always 20-microA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Facilitatory effect of calcium hopantenate on amygdaloid kindling in rats]. 322 34

The neuroligins are a family of proteins that are thought to mediate cell to cell interactions between neurons. During the sequencing at an Xq13 locus associated with a mental retardation syndrome in some studies, we discovered a portion of the human orthologue of the rat neuroligin-3 gene. We now report the structure and the expression of that gene. The gene spans approximately 30kb and contains eight exons. Unlike the rat gene, it codes for at least two mRNAs and at least one of which is expressed outside the CNS. Interestingly, the putative promoter for the gene overlaps the last exon of the neighboring HOPA gene and is located less than 1kb from an OPA element in which a polymorphism associated with mental retardation is found. These findings suggest a possible role for the neuroligin gene in mental retardation and that the role of the gene in humans may differ from its role in rats.
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PMID:The structure and expression of the human neuroligin-3 gene. 1076 52

Weak support for linkage of schizophrenia to proximal Xq has previously been reported. In addition, an increased prevalence of thyroid disorder has been noted in families of individuals with schizophrenia. Recently, a gene mapped to Xq13 termed HOPA has been found to be associated with mental retardation, hypothyroidism, and depression and to function as a coactivator for the thyroid receptor. We therefore examined the HOPA gene in a group of 111 probands from a larger cohort of multiplex families with schizophrenia, several of whom (n = 53) also had a family history of hypothyroidism. Four males and two females were found with an alteration in exon 42 of the HOPA gene compared with 8/492 males and 18/471 females (942 X chromosomes) compared with consecutively screened newborns (chi(2) = 3.92, P < 0.05). However, when available family members of each of the probands with an exon 42 variation were subsequently screened, the mutation did not segregate with schizophrenia in three of five families, although all 6 probands with an exon 42 variation did have hypothyroidism in either themselves (n = 3) or their mothers (n = 3) (P < 0.008). These findings replicate prior findings demonstrating an association between HOPA polymorphisms and hypothyroidism. In addition, the increased frequency of HOPA variants in this population may also provide a genetic basis for the familial association of thyroid disease and schizophrenia.
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PMID:Investigation of a candidate gene for schizophrenia on Xq13 previously associated with mental retardation and hypothyroidism. 1089 21

A recent study suggested that a dodecamer duplication in exon 42 of the HOPA gene in Xq13 may be a significant factor in the etiology of X-linked mental retardation. In an effort to investigate this possibility, we determined the incidence of the dodecamer duplication in cohorts of non-fragile X males with mental retardation from three countries, cohorts of fragile X males from two countries, 43 probands from families with X-linked mental retardation and control cohorts from three countries. The duplication was found in 3.6-4.0% of male patients from two non-fragile X groups (Italy and South Carolina), in 1.2% from another non-fragile X group (South Africa), but in no male patients from families with X-linked mental retardation (South Carolina). The dodecamer duplication was also found in several white males with fragile X syndrome from France (5%) and South Africa (22.2%). Additionally, the duplication was found in 1.5% of South Carolinian newborn males, 2.5% South Carolinian male college students, 5% Italian male controls and 4.5% of the white South African controls. None of the black South African non-fragile X individuals with mental retardation, the fragile X or the control samples tested carried the duplication, suggesting that the duplication is rare in the black South African population. The incidence of the duplication was not significantly different between any of the groups in the study. Therefore, results of our studies in four different populations do not corroborate the findings of the previous study, and indicate that the HOPA dodecamer duplication does not convey an increased susceptibility to mental retardation.
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PMID:Evidence that a dodecamer duplication in the gene HOPA in Xq13 is not associated with mental retardation. 1098 79

The HOPA gene in Xq13 is coding for a protein involved in a nuclear thyroid receptor complex. Previous studies suggested association of the dodecamer duplication in the OPA-repeat region in exon 43 (according to the genomic database sequence) with autism, mental retardation, and schizophrenia/hypothyroidism. We determined the frequency of this 12 bp duplication variant in a sample of 155 patients divided in different subtypes of autism, 278 parents of those patients, and 157 control individuals. The allele frequency of the duplication variant was not significantly different between autistic patients, their parents, and the control group. Therefore, it is unlikely that this 12 bp duplication variant of the HOPA gene has major relevance to the susceptibility to different subtypes of autism at least in this German patient sample. In addition, we identified a third variant with a 15 bp deletion in the OPA-repeat region, recently described by another group, in one autistic patient. This third allele was also present in the patient's nonautistic mother and sister, who are heterozygous for this variant, but could not be detected in any other individual genotyped in this study. Expression analysis revealed transcription of all three allelic variants in lymphoblastoid cell lines. Furthermore, we identified a new splice variant that utilizes an additional 9 bp of the 3' intron subsequent to exon 39. Both alternative transcripts are coexpressed in all fetal and adult tissues examined.
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PMID:Association studies of the HOPA dodecamer duplication variant in different subtypes of autism. 1184 May 15

Variations in exon 42 of the HOPA (human opposite paired) gene have been associated with mental retardation, hypothyroidism and psychiatric disorders. We attempted to replicate the association with schizophrenia using 309 parent-offspring trios from Bulgaria and 367 unrelated cases and 368 blood donors from the UK. We also tested 125 bipolar trios from Bulgaria, 112 bipolar trios from the UK and a sample of 178 unrelated bipolar cases and 188 blood donors from the UK. The frequency of HOPA(12bp) in the 556 UK blood donors was 2.6% and it was not significantly different in the UK patients groups, where it ranged from 1.2 to 3.8%. Sixteen mothers transmitted the HOPA(12bp) allele to schizophrenic offspring, while 12 did not transmit, a non-significant difference. There was a trend for under-transmission of the rare allele to bipolar patients (T/NT = 4/10) and they had a lower rate of that allele than schizophrenic patients in the Bulgarian population (1% vs. 4.2%, P = 0.043). However the two diagnostic groups had similar allele frequencies in the UK populations: 2% versus 2.6%, P = 0.6. We conclude that the HOPA polymorphism is unlikely to be a major risk factor in the pathogenesis of these major psychiatric disorders although there could be a small effect in schizophrenia.
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PMID:Association analysis of the HOPA12bp polymorphism in schizophrenia and manic depressive illness. 1262 58

Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex.
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PMID:A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. 1733 63

The Mediator complex is a fluid assemblage of approximately 25 proteins that is essential for eukaryotic transcriptional regulation. Mediator of RNA polymerase II transcription (MED)12 (HOPA) is a 25-kb Xq13 member of the Mediator complex that plays a key role in the complex and directly moderates receptor tyrosine kinase, nuclear receptor and Wnt pathway signaling. Sequence variation in two MED12 protein domains has been linked to neuropsychiatric illness. First, variants in the Leu-Ser domain have been linked to Opitz-Kaveggia and Lujan syndromes, which are forms of X-linked mental retardation. Second, a balanced polymorphism in the C terminus opposite-paired domain, a key motif in the MED12-mediated transcriptional repression of Wnt signaling, has been associated with increased risk for psychosis. We conclude that variation of MED12 is associated with a wide variety of clinical presentations whose severity is dependent on the location and nature of the variation, and that a thorough understanding of MED12's role in transcriptional regulation could have significant benefits for human healthcare.
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PMID:Role of MED12 in transcription and human behavior. 1771 26

Abnormalities of sex chromosomes are associated with various forms of neuropsychiatric disorders, such as schizophrenia. Turner syndrome occurs approximately threefold more frequently in female schizophrenics compared to the general female population. A single case is reported. We report on a case of a 41-year-old woman with Turner syndrome, schizophrenia, mental retardation, and hypothyroidism. A polymorphism of the HOPA gene within Xq13 termed HOPA(12bp) is associated with schizophrenia, mental retardation, and hypothyroidism. Interestingly, Xq13 is the X-chromosome region that contains the X-inactivation center and a gene escaping X-inactivation whose gene product may be involved in the X-inactivation process as well as in the pathogenesis of sex chromosome anomalies such as Turner syndrome. These genes that escape X-inactivation may produce their gene products in excess, influencing normal brain growth and differentiation. Our case gives a further hint for an involvement of the X-chromosome in the pathogenesis of schizophrenia.
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PMID:Turner syndrome and schizophrenia: a further hint for the role of the X-chromosome in the pathogenesis of schizophrenic disorders. 2021 87

Turner syndrome is a sex-chromosome disorder; occurring in 1 in 2,500 female births. There are sporadic few case reports of concomitant Turner syndrome with schizophrenia worldwide. Most Turner females had a 45,X monosomy, whereas the majority of comorbidity between Turner syndrome and schizophrenia had a mosaic karyotype (45,X/46,XX). We present a case of a 21-year-old woman with Turner syndrome, mosaic karyotype (45,X/46,XX), showing mental retardation, hypothyroidism, and schizophrenia. HOPA gene within Xq13 is related to mental retardation, hypothyroidism, and schizophrenia. Our case may be a potential clue which supports the hypothesis for involvement of genes on X chromosome in development of schizophrenia. Further studies including comorbid cases reports are need in order to discern the cause of schizophrenia in patients having Turner syndrome.
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PMID:Mosaic Turner syndrome associated with schizophrenia. 2492 63


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