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)

Choroideremia is an X chromosome-linked retinal dystrophy of unknown pathogenesis. We have isolated cDNAs from a human retinal library with a genomic probe located at the X chromosomal breakpoint in a female with choroideremia and an X;13 translocation. This cDNA spans the breakpoint in the X;13 translocation female and is deleted in males who have choroideremia as part of a complex phenotype including mental retardation and deafness. However, this cDNA detects no alterations in the DNA of 34 males with isolated choroideremia. Nonetheless, the cDNA does detect reduced or absent levels of mRNA in three-quarters of male patients with an apparently intact gene. These data support the hypothesis that this cDNA represents the gene in which mutations cause choroideremia.
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PMID:Isolation of a candidate gene for choroideremia. 154 74

Cytogenetic analysis of a male infant referred for poor neurological development and failure to thrive showed a microdeletion of the X chromosome, his karyotype being 46,Y,del(X)(pter----q21.1:: q21.2----qter). His mother and grandmother were also found to carry the deletion. DNA probes were used to define the deletion molecularly and it was shown to span intervals 2 to 6 of Cremers et al, a portion of Xq that contains the TCD gene and genes whose absence is associated with deafness and mental retardation. RFLP analysis together with X inactivation studies using the probe M27 beta verified the carrier status of the female relatives and showed non-random X inactivation in the heterozygous females.
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PMID:Molecular and cytogenetic analysis of a familial microdeletion of Xq. 167 84

We have localized a single-copy DNA probe, HU16 (locus DXS26), to Xq21.1. The probe was isolated from a human-mouse hybrid X;13 library and mapped with human-mouse hybrids containing different portions of the human X chromosome and DNA from male patients with different X-chromosomal deletions. The following order of loci is proposed: Xcen-(DXS72,DXS169)-(DXS232,DSX26)-DXS1 21-DXS233-DXS165-TCD-DXS95-DXYS1-Xqter. HU16 will be useful in the study of the putative genes that reside in Xq21 and whose defects lead to deafness and mental retardation.
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PMID:DXS26 (HU16) is located in Xq21.1. 216 4

Characterization of several male-viable deletions and duplications with 20 random DNA probes has enabled us to subdivide the Xq21 region into seven discernible intervals. Almost all of the deletions spanning part of Xq21 are associated with choroideremia and mental retardation, with deafness being another common feature. The gene locus for choroideremia was assigned to interval 3 spanning the loci DXS95, DXS165, and DXS233. Genes for X-linked deafness and mental retardation were tentatively assigned to interval 2. Deletions of intervals 4 through 7 were not associated with any clinical abnormality. We have constructed a preliminary long-range restriction map of intervals 2 and 3 using field-inversion gel electrophoresis. The DXS232, DXS121, and DXS233 loci are located on the same SfiI fragment, whereas the DXS165 and DXS95 loci could not be linked to this cluster using SfiI and SalI.
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PMID:Physical fine mapping of the choroideremia locus using Xq21 deletions associated with complex syndromes. 291 8

An interstitial deletion of the proximal part of the long arm of the X chromosome was found in two brothers both suffering from choroideremia, congenital deafness and mental retardation. The mother was subsequently found to be heterozygous for the deletion, and to have the typical ophthalmological phenotype of a choroideremia carrier together with an elevated stapedial reflex threshold. Syndromes including choroideremia seem to be composed of characteristics which, independent of each other, occur as X-linked traits. Since this deletion covers part of the region Xq21.1-Xq21.31 it is postulated that besides the locus for choroideremia this region harbors a locus for X-linked congenital deafness and possibly a locus for X-linked mental retardation.
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PMID:Choroideremia, congenital deafness and mental retardation in a family with an X chromosomal deletion. 343 52

Choroideremia, an X-chromosome linked retinal dystrophy of unknown pathogenesis, causes progressive nightblindness and eventual central blindness in affected males by the third to fourth decade of life. Choroideremia has been mapped to Xq13-21 by tight linkage to restriction fragment length polymorphism loci. We have recently identified two families in which choroideremia is inherited with mental retardation and deafness. In family XL-62, an interstitial deletion in Xq21 is visible by cytogenetic analysis and two linked anonymous DNA markers, DXYS1 and DXS72, are deleted. In the second family, XL-45, an interstitial deletion was suspected on phenotypic grounds but could not be confirmed by high-resolution cytogenetic analysis. We used phenol-enhanced reassociation of 48,XXXX DNA in competition with excess XL-45 DNA to generate a library of cloned DNA enriched for sequences that might be deleted in XL-45. Two of the first 83 sequences characterized from the library were found to be deleted in probands from family XL-45 as well as from family XL-62. Isolation of these sequences proves that XL-45 does contain a submicroscopic deletion and provides a starting point for identifying overlapping genomic sequences that span the XL-45 deletion. Each overlapping sequence will be studied to identify exons from the choroideremia locus.
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PMID:Isolation of anonymous DNA sequences from within a submicroscopic X chromosomal deletion in a patient with choroideremia, deafness, and mental retardation. 347 58

We have found that the microsatellite marker AFM207zg5 (DXS995) maps to all previously described deletions which are associated with X-linked mixed deafness (DFN3) with or without choroideremia and mental retardation. Employing this marker and pHU16 (DXS26) we have identified two partially overlapping yeast artificial chromosome clones which were used to construct a complete 850 kb cosmid contig. Cosmids from this contig have been tested by Southern blot analysis on DNA from 16 unrelated males with X-linked deafness. Two novel microdeletions were detected in patients which exhibit the characteristic DFN3 phenotype. Both deletions are completely contained within one of the known DFN3-deletions, but one of them does not overlap with two previously described deletions in patients with contiguous gene syndromes consisting of DFN3, choroideremia, and mental retardation. Assuming that only a single gene is involved, this suggests that the DFN3 gene spans a chromosomal region of at least 400 kb.
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PMID:X-linked mixed deafness (DFN3): cloning and characterization of the critical region allows the identification of novel microdeletions. 798 85

Microscopically detectable deletions and X;autosome translocations have previously facilitated the construction of a high-resolution interval map of the Xq21 region. Here, we have generated three yeast artificial chromosome contigs spanning approximately 7 megabases of the Xq13.3-q21.31 region. In addition, a novel deletion associated with choroideremia and mental retardation was identified and mapped in detail. The proximal deletion endpoint was positioned between the loci DXS995 and DXS232, which enabled us to confirm the critical region for a locus involved in mental retardation. The distal deletion endpoint is situated in the Xq21.33 band, which allowed us to refine the order of several markers in this region.
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PMID:Yeast artificial chromosome cloning of the Xq13.3-q21.31 region and fine mapping of a deletion associated with choroideremia and nonspecific mental retardation. 852 69

Genetic studies in families with X linked mental retardation have suggested the location of several MR genes in the human q21 region. Since the establishment of cloned resources is an essential step towards the cloning of genes involved in inherited diseases, we built a yeast artificial chromosome (YAC) contig and an STS map of this part of the X chromosome. The contig, which extends from PGK1 in Xq13.3 to DXS1002 in Xq21.2, consists of 30 YACs mapped with 21 markers and spans about 6 Mb. The YAC contig was used as a framework to localise several previously known genes and CEPH/Genethon polymorphic markers, as well as to construct a physical map of the region surrounding one of these genes. We recently localised a presumed MR locus to the region flanked by DXS233 (proximal) and CHM (distal). In the present work, the zinc finger gene, ZNF6, has been shown to lie within this region and to be highly expressed in brain, making it a good candidate MR gene. Similarly the VDAC1 gene has been mapped between DXS986 and DXS72 and its candidate gene status for the Allan-Herndon-Dudley syndrome is discussed.
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PMID:Localisation of two candidate genes for mental retardation using a YAC physical map of the Xq21.1-21.2 subbands. 873 41

A YAC/STS map has been assembled spanning 22 Mb across Xq12-q21.31, between markers DXS1125 and DXS95. In addition to the landmark loci for the X-inactivation center XIST and the ATRX, ATP7A, phosphoglycerate kinase, POU3F4, and choroideremia genes, the candidate disease gene regions for torsion dystonia 3 and two X-linked mental retardation syndromes are included. Also, the human voltage-dependent anion channel gene (HVDAC1) has been placed near DXS986. The current map incorporates 211 YACs from five different libraries, formatted with 185 STSs that comprise 26 genetic linkage markers, 60 newly-developed YAC-end STSs, and eight ESTs. The multiple clone coverage and average resolution of one STS per 120 kb provide resources for disease gene searches and are facilitating complete sequencing of the region.
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PMID:22-Mb integrated physical and genetic map based on YAC/STS content spanning the interval DXS1125-DXS95 in human Xq12-q21.31. 952 53


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