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)

Four cases of oculodentodigital dysplasia are reported. Three cases are from the same family, father and two daughers. These three cases have the characteristics typical of this disorder: narrow nose, hypoplastic alae nasi, microphthalmia, defects of the teeth, syndactylyl of the IV and V fingers, and skeletal anomalies. The fourth case differs from the earlier reported cases; he has all the typical findings of oculodentodigital dysplasia but in addition he shows features not previously reported, namely exceptionally poor vision, mental retardation, monilethrix and pili annuli changes of the hair.
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PMID:Oculodentodigital dysplasia syndrome. Report of four cases. 19 79

We describe 3 young children with Hallermann-Streiff syndrome, 2 with typical manifestations and 1 with the facial changes without the eye abnormalities but with a cleft palate and with complete syndactyly of fingers IV and V. The latter case represents overlap of the Hallermann-Streiff syndrome and oculodentodigital dysplasia. "Dwarfism" as a possible clinical risk marker of mental retardation is discussed. As cause, a mendelian autosomal dominant mutation seems most probable.
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PMID:Hallermann-Streiff syndrome: clinical and psychological findings in children. Nosologic overlap with oculodentodigital dysplasia? 166 4

During embryonic development, young neurons migrate from the ventricular zone to the cortical plate of the cerebral cortex. Disturbances in this neuronal migration have been associated with numerous diseases such as mental retardation, double cortex, Down syndrome, and epilepsy. One possible cause of these neuropathologies is an aberration in normal gap junctional communication. At least 20 connexin (Cx) genes encode gap junction proteins in mice and humans. A proper understanding of the role of specific connexins in the developing brain requires the characterization of their spatial and temporal pattern of expression. In the current study we performed all the experiments on mouse developing cortex at embryonic days (E) 14, 16, and 18, timepoints that are highly active with regard to cortical development. Using reverse transcription-polymerase chain reaction, Western blot analysis, and immunohistochemistry, we found that among the family of gap junction proteins, Cx26, Cx36, Cx37, Cx43, and Cx45 were expressed in the developing cortex of mice, Cx30 and Cx32 were absent, while Cx40 was expressed at a very low level. Our results demonstrate that Cx26 and Cx37 were evenly distributed in the cortical layers of developing brain, while Cx36 and Cx43 were more abundant in the ventricular zone and cortical plate. Cx45 distribution appeared to be more abundant at E18 compared to the other timepoints (E14 and E16). Thus, the present study provides identification and the distribution pattern for Cxs associated with cortical development during normal neuronal migration.
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PMID:Expression of connexins in embryonic mouse neocortical development. 1764 36

Oculo-dento-digital dysplasia (ODDD) is an autosomal dominant disorder with complete penetrance and high intra- and interfamilial phenotypic variability. The key features in this syndrome are microphthalmia, enamel hypoplasia and syndactyly of the 4th-5th fingers. ODDD is caused by mutations in the connexin 43 gene (GJA1). We report here four patients from three families with GJA1 mutations, one of them diagnosed prenatally. The three mutations (c.52T > C/p.Ser18Pro, c.689_690delTA/p.Tyr230CysfsX6, c.442C > G/p.Arg148Gly) have been reported once before. Two patients had white matter hypersignal anomalies, associated in one case with mental retardation, but asymptomatic in the other one, an observation that leads us to discuss systematic neuroradiological imaging for ODDD. One case has optic atrophy, another has hypospadias. The patient carrying a truncating mutation of Cx43 did not have palmoplantar keratoderma, in contradiction with the previously suggested genotype-phenotype correlation between truncating mutation and skin involvement.
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PMID:Oculo-dento-digital dysplasia: lack of genotype-phenotype correlation for GJA1 mutations and usefulness of neuro-imaging. 1980 3

Robert syndrome (RBS) and Cornelia de Lange syndrome (CdLS) are human developmental disorders characterized by craniofacial deformities, limb malformation and mental retardation. These birth defects are collectively termed cohesinopathies as both arise from mutations in cohesion genes. CdLS arises due to autosomal dominant mutations or haploinsufficiencies in cohesin subunits (SMC1A, SMC3 and RAD21) or cohesin auxiliary factors (NIPBL and HDAC8) that result in transcriptional dysregulation of developmental programs. RBS arises due to autosomal recessive mutations in cohesin auxiliary factor ESCO2, the gene that encodes an N-acetyltransferase which targets the SMC3 subunit of the cohesin complex. The mechanism that underlies RBS, however, remains unknown. A popular model states that RBS arises due to mitotic failure and loss of progenitor stem cells through apoptosis. Previous findings in the zebrafish regenerating fin, however, suggest that Esco2-knockdown results in transcription dysregulation, independent of apoptosis, similar to that observed in CdLS patients. Previously, we used the clinically relevant CX43 to demonstrate a transcriptional role for Esco2. CX43 is a gap junction gene conserved among all vertebrates that is required for direct cell-cell communication between adjacent cells such that cx43 mutations result in oculodentodigital dysplasia. Here, we show that morpholino-mediated knockdown of smc3 reduces cx43 expression and perturbs zebrafish bone and tissue regeneration similar to those previously reported for esco2 knockdown. Also similar to Esco2-dependent phenotypes, Smc3-dependent bone and tissue regeneration defects are rescued by transgenic Cx43 overexpression, suggesting that Smc3 and Esco2 cooperatively act to regulate cx43 transcription. In support of this model, chromatin immunoprecipitation assays reveal that Smc3 binds to a discrete region of the cx43 promoter, suggesting that Esco2 exerts transcriptional regulation of cx43 through modification of Smc3 bound to the cx43 promoter. These findings have the potential to unify RBS and CdLS as transcription-based mechanisms.
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PMID:Cohesin mediates Esco2-dependent transcriptional regulation in a zebrafish regenerating fin model of Roberts Syndrome. 2908 13