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)

Mutations of the transcription factor 4 (TCF4) gene cause mental retardation with or without associated facial dysmorphisms and intermittent hyperventilation. Subsequently, a polymorphism of TCF4 was shown in a genome-wide association study to slightly increase the risk of schizophrenia. We have further analysed the impact of this TCF4 variant rs9960767 on early information processing and cognitive functions in schizophrenia patients. We have shown in a sample of 401 schizophrenia patients that TCF4 influences verbal memory in the Rey Auditory Verbal Learning Test. Contrary to expectations, carriers of the schizophrenia-associated allele showed better recognition, thus indicating that while TCF4 influences verbal memory, the TCF4-mediated schizophrenia risk is not determined by the influence of TCF4 on verbal memory. TCF4 does not impact on various other cognitive functions belonging to the domains of attention and executive functions. Moreover, in a pharmacogenetic approach, TCF4 does not modulate the improvement of positive or negative schizophrenia symptoms during treatment with antipsychotics. Finally, we have assessed a key electrophysiological endophenotype of schizophrenia, sensorimotor gating. As measured by prepulse inhibition, the schizophrenia risk allele C of TCF4 rs9960767 reduces sensorimotor gating. This indicates that TCF4 influences key mechanisms of information processing, which may contribute to the pathogenesis of schizophrenia.
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PMID:Impact of TCF4 on the genetics of schizophrenia. 2193 83

PTEN gene (phosphatase and tensin homolog deleted on chromosome ten, MIM 601628) is a tumor suppressor gene implicated in PTEN hamartoma tumor syndromes (PHTS) including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome and Proteus-like syndrome. PTEN mutations have been more recently reported in children with macrocephaly and autism spectrum disorders or mental retardation, without other symptoms of PHTS. Although tumor risk has not been evaluated in these patients and their relatives, the same surveillance as for Cowden syndrome is usually proposed. We report a family including patients carrying a novel PTEN mutation and presenting with a mild phenotype consisting of macrocephaly, hypotonia during the first year of life and mild learning disabilities, without autistic features. None of these patients exhibited PTHS-related symptoms such as tumors, lipomas, vascular malformations or pigmented macules of the glans penis. This report raises the question of extending the indications of PTEN mutation screening to familial macrocephaly with learning disabilities. Detection of a mutation in this family led to difficult questions about surveillance, genetic counseling and familial information since the mother declined tumor screening and disclosure of genetic risk information to at-risk relatives.
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PMID:Novel PTEN germline mutation in a family with mild phenotype: difficulties in genetic counseling. 2312 40

The Pitt-Hopkins syndrome is a very rare and severe genetic disease characterized by mental retardation, psychomotor and developmental delays with facial dysmorphism. It was first described in 1978 in patients with mental retardation and crisis of intermittent hyperventilation. The genetic cause is haploinsufficiency of the TCF4 (transcription factor 4) gene that affects the neurodevelopment in both sexes; the majority of patients have spontaneous molecular defects by point mutations or deletions in chromosome 18 at the region 18q21. The syndrome is characterized by neurological abnormalities that affect the motor coordination and balance, in patients with mental and developmental delays. The phenotype includes a peculiar face by specific craniofacial anomalies: prominent square forehead, deep-set eyes with ocular hypertelorism; prominent large nose beaked and broad flat nasal bridge; mouth wide and large, thick fleshy lips, tented bow-shaped upper lip and everted lower lip; cup-shaped ears with dysplastic broad overfolded helix. We review the literature and the photographs of 44 published patients from 2007 to 2012, to resume the principal features of craniofacial anomalies, attempting to delineate the syndrome phenotype and score the specific dysmorphism than help to achieve the early clinical diagnosis.
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PMID:Pitt-Hopkins syndrome: Mental retardation, psychomotor and developmental delays with facial dysmorphism. 2762 70