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)

Schizophrenia, a severe neuropsychiatric disorder, is believed to involve multiple genetic factors. A significant body of evidence supports a pivotal role for abnormalities of brain development in the disorder. Linkage signals for schizophrenia map to human chromosome 6q. To obtain a finer localization, we genotyped 180 single nucleotide polymorphisms (SNPs) in a young, inbred Arab-Israeli family sample with a limited number of founders. The SNPs were mostly within a approximately 7 Mb region around the strong linkage peak at 136.2 Mb that we had previously mapped. The most significant genetic association with schizophrenia for single SNPs and haplotypes was within a 500 kb genomic region of high linkage disequilibrium (LD) at 135.85 Mb. In a different, outbred, nuclear family sample that was not appropriate for linkage analysis, under-transmitted haplotypes incorporating the same SNPs (but not the individual SNPs) were significantly associated with schizophrenia. The implicated genomic region harbors the Abelson Helper Integration Site 1 (AHI1) gene, which showed the strongest association signal, and an adjacent, primate-specific gene, C6orf217. Mutations in human AHI1 underlie the autosomal recessive Joubert Syndrome with brain malformation and mental retardation. Previous comparative genomic analysis has suggested accelerated evolution of AHI1 in the human lineage. C6orf217 has multiple splice isoforms and is expressed in brain but does not seem to encode a functional protein. The two genes appear in opposite orientations and their regulatory upstream regions overlap, which might affect their expression. Both, AHI1 and C6orf217 appear to be highly relevant candidate genes for schizophrenia.
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PMID:AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia. 1677 25

Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital muscular dystrophy associated with brain and eye abnormalities. WWS has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years. WWS presents at birth with generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. It is associated with type II cobblestone lissencephaly, hydrocephalus, cerebellar malformations, eye abnormalities and congenital muscular dystrophy characterized by hypoglycosylation of alpha-dystroglycan. Several genes have been implicated in the etiology of WWS, and others are as yet unknown. Several mutations were found in the Protein O-Mannosyltransferase 1 and 2 (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related protein (FKRP) genes. Laboratory investigations usually show elevated creatine kinase, myopathic/dystrophic muscle pathology and altered alpha-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown. No specific treatment is available. Management is only supportive and preventive.
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PMID:Walker-Warburg syndrome. 1688 26

Rubinstein-Tabyi Syndrome (RTS) is characterized by broad toes, broad thumbs, facial dysmorphisms, and mental retardation. The syndrome has been shown in some patients to be associated with break points in and microdeletions of chromosome 16p13.3. It is estimated that approximately 75% of patients with RTS experience recurrent respiratory infections. In this study, three patients thought to have RTS and recurrent infections were evaluated for an immunologic deficiency. All three patients showed a polysaccharide antibody response deficit. We conclude that a primary immune deficiency may exist in the remainder of the RTS population and may explain the reason for the propensity for recurrent infections. Aggressive investigation and management in patients with RTS may further determine the mechanism of this deficiency and enhance the quality of life of these patients.
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PMID:Rubinstein-Taybi syndrome: an immune deficiency as a cause for recurrent infections. 1691 74

To examine the behavioral and emotional difficulties of 73 children and adolescents with Prader-Willi Syndrome (PWS), mental retardation-only, and dual diagnosis (i.e., mental retardation and psychiatrically disordered) on the Devereux Scales of Mental Disorders (DSMD: Naglieri, LeBuffe, & Pfeiffer, Devereux Scales of Mental Disorders (DSMD) San Antonio, TX: PsychCorp 1994). Multivariate analyses and "Italic">d-ratios were computed to assess the statistical and clinically meaningful differences between pairs of samples. The PWS sample exhibited statistically significant higher levels of psychopathology than the mentally-retarded-only sample on the Total, Externalizing, Internalizing, Attention/Delinquency, Conduct, Anxiety, and Acute Problems Scales. When compared to the dually-diagnosed sample, children with PWS Syndrome had comparable levels of psychopathology, but lower levels of depression. Results revealed that PWS represents a highly unique and complex psychological disorder with multiple areas of disturbances.
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PMID:Behavioral and emotional symptoms of children and adolescents with Prader-Willi Syndrome. 1694 Dec 27

Pallister-Killian Syndrome (PKS) is a rare sporadic congenital anomaly disorder, characterized by multiple congenital anomalies, especially craniofacial dysmorphism. It is also associated with mental retardation, seizure, skin pigmentation, and visceral malformations such as congenital diaphragmatic hernia, congenital heart defect, anorectal anomalies, and genital malformation. This syndrome usually presents with tissue-limited mosaicism of supernumerary 12p isochromosome i (12p). Moreover, diagnosis of Pallister-Killian Syndrome (PKS) is difficult because the ratio of abnormal to normal karyotyping is much lower in peripheral lymphocytes than in skin fibroblasts. We report the first case in Taiwan, who has tetrasomy 12p mosaic in peripheral lymphocytes.
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PMID:Pallister-Killian syndrome: report of one case. 1707 67

Opitz G/BBB Syndrome (OS) is a multiple congenital anomaly disorder characterized by defects along the body midline. The disease is characterized by variable expressivity of signs that include hypertelorism, cleft lip and/or palate, laryngo-tracheo-esophageal abnormalities, cardiac defects, and hypospadias. OS patients also present with mental retardation and brain anatomical abnormalities. An autosomal dominant form mapping to chromosome 22 and an X-linked form of OS are known. The gene responsible for the X-linked form of OS, MID1, codes for a member of the Tripartite Motif family of E3 ubiquitin ligases. Here we report 29 novel mutations in 29 unrelated patients of a cohort of 140 male OS cases. These mutations are found in both familial and sporadic cases. They are scattered along the entire length of the gene and are represented by missense and nonsense mutations, insertions and deletions causing frame shift mutations, and deletion of either single exons or the entire gene. The variety of the mutations found confirms that loss-of-function is the mechanism underlying the OS phenotype. Moreover, the low percentage of MID1-mutated OS patients, 47% of the familial and 13% of the sporadic cases, suggests a wider genetic heterogeneity underlying the OS phenotype.
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PMID:MID1 mutation screening in a large cohort of Opitz G/BBB syndrome patients: twenty-nine novel mutations identified. 1722 65

The biosynthesis and metabolism of cholesterol in the brain is spatiotemporally and developmentally regulated. Brain cholesterol plays an important role in maintaining the function of neuronal receptors, which are key components in neural signal transduction. This is illustrated by the requirement of membrane cholesterol for the function of the serotonin(1A) receptor, a transmembrane neurotransmitter receptor. A crucial determinant for the function of neuronal receptors could be the availability of brain cholesterol. The Smith-Lemli-Optiz Syndrome, a metabolic disorder characterized by severe neurodegeneration leading to mental retardation, represents a condition in which the availability of brain cholesterol is limited. A comprehensive molecular analysis of lipid-protein interactions in healthy and diseased states could be crucial for a better understanding of the pathogenesis of psychiatric disorders.
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PMID:Lipid-protein interactions, regulation and dysfunction of brain cholesterol. 1725 51

Hypoparathyroidism-retardation-dysmorphism (HRD; Sanjad-Sakati Syndrome; Online Mendelian Inheritance in Man [OMIM] #241410) is a rare recessive syndrome predominantly seen on the Arabian Peninsula and characterized by congenital hypoparathyroidism, intrauterine growth retardation, mental retardation, seizures, and a typical facial dysmorphism (prominent forehead, deep-set eyes, and abnormal external ears).(1,2) To date, the same homozygous deletion in TBCE (155-166del) has been reported in all Saudi Arabian patients with HRD(1) as well as in all Saudi Arabian patients with Kenny-Caffey syndrome (OMIM #244460),(1) a syndrome with a phenotype that resembles that of HRD but is characterized by the presence of normal intelligence, late closure of the anterior fontanelle, macrocephaly, and postnatal (rather than prenatal) growth retardation.(1,3) Nanophthalmos and corneal opacity have been documented in Kenny-Caffey syndrome patients,(4) but ocular disease has not been well-described in HRD. We describe the ocular features of four Saudi Arabian HRD children referred to our institution for ocular complaints noted by their parents.
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PMID:Ophthalmic features of hypoparathyroidism-retardation-dysmorphism. 1725 73

Within the developing mammalian CNS, growth factors direct multipotent precursors to generate neurons versus glia, a process that if perturbed might lead to neural dysfunction. In this regard, genetic mutations resulting in constitutive activation of the protein tyrosine phosphatase SHP-2 cause Noonan Syndrome (NS), which is associated with learning disabilities and mental retardation. Here, we demonstrate that genetic knockdown of SHP-2 in cultured cortical precursors or in the embryonic cortex inhibited basal neurogenesis and caused enhanced and precocious astrocyte formation. Conversely, expression of an NS SHP-2 mutant promoted neurogenesis and inhibited astrogenesis. Neural cell-fate decisions were similarly perturbed in a mouse knockin model that phenocopies human NS. Thus, SHP-2 instructs precursors to make neurons and not astrocytes during the neurogenic period, and perturbations in the relative ratios of these two cell types upon constitutive SHP-2 activation may contribute to the cognitive impairments in NS patients.
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PMID:Control of CNS cell-fate decisions by SHP-2 and its dysregulation in Noonan syndrome. 1744 46

Seckel syndrome is an autosomal recessive disease presenting with microcephalic dwarfism, mental retardation and facial and skeletal abnormalities. Morgagni hernia is quite rare, constituting 1-6% of all diaphragmatic hernias. It is asymptomatic, especially in childhood. Morgagni hernia has never been reported in patients with Seckel Syndrome. Here we report a 3-year-old boy diagnosed as having Seckel Syndrome with Morgagni hernia, which has to be considered during physical examination of patients.
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PMID:Seckel syndrome with Morgagni hernia. 1755 41


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