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)

Historically, mankind has at least suspected that alcohol was somehow connected with undesirable effects on progeny. In the 18th century, physicians became aware that maternal alcohol consumption resulted in excess fetal and neonatal mortality, low birth weight, and many other deleterious effects. Perhaps as a response to the temperance and Prohibition periods, scientists lost sight of or interest in the effects of alcohol in pregnancy. In the late 1960s and early 1970s, the issue surfaced again, and scientists began systematic and in-depth studies of fetal alcohol syndrome (FAS) and alcohol-related birth defects (ARBD). Epidemiologic research now suggests that FAS has outranked Down's syndrome and spina bifida in prevalence and is now the leading known cause of mental retardation. Further, it is the only one of these three that is preventable. Because a safe limit of alcohol consumption in pregnancy is not defined, abstinence during pregnancy is the most prudent preventive measure. Factors such as race, beer drinking, maternal weight gain, and low socioeconomic status are associated with a statistical increase in the incidence of FAS. In families where one child has been diagnosed as having FAS, the incidence rate can be as much as 405-fold higher than the worldwide average. Neurobehavioral deficits can occur in the offspring of drinking mothers in the absence of a diagnosis of full FAS. The deficits differ with age and seem to persist into adulthood. Mental retardation or borderline mental retardation is a nearly ubiquitous neurological deficit in diagnosed FAS. In one study, it occurred in 75 percent of the non-FAS offspring of mothers who continued to drink heavily throughout their pregnancy.From the mid-1970s, having established that alcohol is a teratogen, scientists have been trying to uncover the mechanism by which alcohol exerts its embryotoxic effects. Recent promising neuroanatomical studies have demonstrated that alcohol has a deleterious effect on neuronal migration and hence on the development of the cerebral cortex. Other studies have shown that prenatal alcohol exposure,by adversely affecting hippocampal development,may be responsible for the learning deficits so frequently encountered in FAS children. Other research has implicated prostaglandins in the mechanism of alcohol-related dysmorphology.
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PMID:Alcohol-related birth defects: an update. 314 58

A 16-year-old boy with classical phenylketonuria (PKU) and mild mental retardation (IQ 69) was detected by the screening of mentally retarded school children in Taiwan with Guthrie's bacterial inhibition assay. The follow-up family study showed that one of his married elder sisters suffered from borderline mental retardation (IQ 75) and was also diagnosed as a classical case of PKU. She had borne one boy and one girl, both suffering from mild mental retardation, microcephaly, delay in linguistic development and severe growth retardation. This is the first known Chinese family with maternal PKU. To prevent future mental retardation caused by maternal PKU, the simultaneous establishment of a register system with a neonatal screening programme, is indicated for the follow-up of PKU girls, screening of the whole family of newly discovered PKU cases, and to exclude unrecognized maternal PKU in women who have given birth to a microcephalic child.
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PMID:A Chinese family with phenylketonuria and maternal phenylketonuria detected by family screening. 379 88

Thirty-four children (ages 6-12 years) with moderate to borderline mental retardation were studied in a laboratory classroom setting to determine whether children identified as having attention deficit hyperactivity disorder on the basis of Conners Questionnaires differed in classroom behavior. Half of the children scored 15 or greater on both the Parent and Teacher Conners; the remaining children scored 11 or less. All were participants in a Saturday Education Program serving children with mental retardation. Direct observation of the laboratory classroom documented significant differences between groups on measures of on-task behavior and fidgetiness, especially during situations where little direct teacher feedback or supervision was available. Saturday Education Program staff, while blind as to group designation, rated the two groups as differing significantly on all scales of two standardized behavior problem checklists. Checklists by parents and teachers appear to be valid measures of classroom behavior of children with moderate to borderline mental retardation.
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PMID:Classroom behavior and children with mental retardation: comparison of children with and without ADHD. 806 33

The reliability of diagnoses of mental retardation severity was examined through the comparison of psychiatric and psychological case reports found in client records. For a sample of 126 dually diagnosed clients, overall chance-corrected agreement was .47, ranging from .38 (for diagnoses of moderate mental retardation) to .55 (for diagnoses of borderline mental retardation). Results showed that the analysis of naturally occurring variation in diagnostic practices (including variability in professional judgment and assessment methods) may offer a more realistic appraisal of the reliability of diagnostic decisions in professional practice situations than do studies in which important sources of diagnostic error are controlled.
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PMID:Reliability of psychiatric and psychological diagnoses of mental retardation severity: judgments under naturally occurring conditions. 846 Nov 26

Monoamine oxidase (MAO) exists as two isoenzymes and plays a central role in the metabolism of monoamine neurotransmitters. In this study we compared the neurochemical phenotypes of previously described subjects with genetically determined selective lack of MAO-A or a lack of both MAO-A and MAO-B with those of two subjects with a previously described X chromosome microdeletion in whom we now demonstrate selective MAO-B deficiency. Mapping of the distal deletion breakpoint demonstrates its location in intron 5 of the MAO-B gene, with the deletion extending proximally into the Norrie disease gene. In contrast to the borderline mental retardation and abnormal behavioral phenotype in subjects with selective MAO-A deficiency and the severe mental retardation in patients with combined MAO-A/MAO-B deficiency and Norrie disease, the MAO-B-deficient subjects exhibit neither abnormal behavior nor mental retardation. Distinct neurochemical profiles characterize the three groups of MAO-deficient patients. In MAO-A-deficient subjects, there is a marked decrease in deaminated catecholamine metabolites and a concomitant marked elevation of O-methylated amine metabolites. These neurochemical changes are only slightly exaggerated in patients with combined lack of MAO-A and MAO-B. In contrast, the only biochemical abnormalities detected in subjects with the MAO-B gene deletion are a complete absence of platelet MAO-B activity and an increased urinary excretion of phenylethylamine. The differences in neurochemical profiles indicate that, under normal conditions, MAO-A is considerably more important than MAO-B in the metabolism of biogenic amines, a factor likely to contribute to the different clinical phenotypes.
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PMID:Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes. 861 23

Nonspecific X-linked mental retardation (XLMR) is a common disorder. The number of genes involved in this condition is not known, but it is estimated to be more than 10. We present a clinical and linkage study on 3 families with XLMR. All families were analyzed using highly polymorphic markers covering the X chromosome; screening for the fragile X mutation was negative. The first family (MRX 36) consisted of 1 female and 4 male patients in 3 generations and 7 healthy individuals. Considering the female as an expressing heterozygous carrier, a maximum LOD score of 3.41 was reached in region Xp21.2-Xp22.1. Considering her phenotype to be unknown, a LODmax of 1.97 was reached in the same region. The second family consisted of 5 affected and 6 healthy males with mild to borderline mental retardation. Linkage analysis using an X-linked recessive model with full penetrance and no phenocopies excluded linkage over almost the entire X chromosome. Using alternative models, including an affecteds-only analysis, a LODmax of 1.49 was found in region Xq24-28. The third family, consisting of 4 male patients with moderate mental retardation in 1 generation yielded a LODmax of 0.9 in region Xp22.13-11.3. However, even in this small pedigree, exclusion mapping was able to exclude very large parts of the X chromosome and in this way identify a likely candidate region.
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PMID:Linkage analysis in three families with nonspecific X-linked mental retardation. 1237 49

Two families with nonspecific X-linked mental retardation (MRX) are presented. In the first family, MRX51, three male patients showed mild to borderline mental retardation. Multipoint linkage analysis yielded a maximal LOD score of 2.10 between markers DXS8012 and DXS1003, localizing the MRX51 gene at Xp11.3-p11.23. In the second family, XLMR7, three men showed moderate mental retardation (MR), and one possible female carrier had mild MR. Multipoint linkage analysis yielded an LOD score of 1.80 between markers DXS8063 and DXS1047, situating the disease gene at Xq23-q26.1. When the analysis was performed considering the affected female to be an expressing heterozygote carrier of the disease mutation, a maximal LOD score of 2.10 was found in the same region.
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PMID:Regional localization of a gene for nonspecific XLMR to Xp11.3-p11. 23 (MRX51) and tentative localization of an MRX gene to Xq23-q26.1. 1039 44

Expansion of the FRAXE CCG repeat to a full mutation is associated with methylation and transcriptional silencing of the FMR2 gene, and as a consequence, mild-to-borderline mental retardation. FMR2 is a member of a family of four proteins, AF4, LAF4, FMR2, and AF5q31. The proteins associated with this family localize to the cell nucleus. Various regions of FMR2, and each of the other members of the protein family, were cloned and analyzed for transcription activation in yeast and mammalian cells. In both yeast and mammalian cells, FMR2 showed strong transcription activation. AF4 activation potential was several-fold lower. Interestingly, isoforms of both FMR2 and LAF4 lacking exon 3 activated transcription better than the larger isoforms containing exon 3. Compared with the other members of the family, activation by FMR2 was the strongest. Our results show that FMR2 is a potent transcription activator and that its function is conserved. Elucidation of the function of the FMR2 protein as a transcription activator may place FMR2 within the molecular signalling pathways involved in nonspecific X-linked mental retardation (MRX).
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PMID:Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator. 1135 14

Pathological self-mutilation is defined as a deliberate destruction of body tissue without conscious intent. It is sometimes associated with several pathologies such as mental disorders and mental retardation. We report a non-psychotic male, with borderline mental retardation who practiced sporadic moderate genital self-mutilations as a masturbation technique and presented as a case of recurrent gross hematuria.
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PMID:[Male genital self mutilation--a cause of hematuria]. 1148 57

Ring chromosomes are thought to be the result of breakage in both arms of a chromosome, with fusion of the points of fracture and loss of the distal fragments. Another mechanism of ring formation is believed to be the simple fusion of chromosome ends with preservation of telomeric and subtelomeric sequences. Ring chromosome 13 was first described in 1968 and its incidence estimated at 1 in 58,000 live births. Severe phenotypes associated with large deletions of 13q have been described as "ring chromosome 13 syndrome." Features of the "ring chromosome 13 syndrome" include mental retardation (often severe), growth retardation, microcephaly, facial dysmorphism, and hand, foot or toe abnormalities. We report on a case of a mother and daughter with r(13) and mild phenotypes. Our patient, IA, had chromosome analysis performed at about 4(1/2) years of age due to some developmental delay. This revealed 46,XX, r(13)(p13q34) karyotype with no loss of any chromosomal band. Her mother, EA, was subsequently found to have the same ring 13. IA's maternal grandmother had a normal karyotype while her maternal grandfather was unavailable for testing. Fluorescence in situ hybridization (FISH) analysis showed loss of a specific subtelomeric 13q region in r(13) in the mother. Clinically, IA had macular hyperpigmentation on the chin and mild delay in speech and fine motor skills. EA, 22 years of age, had mild short stature and borderline mental retardation. To our knowledge, this is the first report of a case of familial transmission of r(13). We compare phenotypes of our cases with those from other reported cases of r(13) and discuss the possible mechanism of formation of this ring chromosome.
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PMID:Transmission of ring chromosome 13 from a mother to daughter with both having a 46,XX, r(13)(p13q34) karyotype. 1532 36


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