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)

A large family with non-specific X-linked mental retardation (MRX) was first described in 1991 [Glass et al., 1991], with a suggestion of linkage to Xq26-27. The maximum lod score was 1.60 (theta = 0.10) with the F9 locus. The localisation of this MRX gene has now been established by linkage to microsatellite markers. Peak pairwise lod scores of 4.02 and 4.01 (theta = 0.00) were attained at the DXS1114 and DXS994 loci respectively. This MRX gene is now designated MRX27 and is localised to Xq24-26 by recombination events detected by DXS424 and DXS102. This regional localisation spans 26.2 cM on the genetic background map and defines another distinct MRX interval by linkage to a specific region of the X chromosome.
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PMID:Genetic localisation of MRX27 to Xq24-26 defines another discrete gene for non-specific X-linked mental retardation. 882 61

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

Although genotype-phenotype correlations in male patients with various types of nullisomy for Xp22.3 have assigned a locus for X-linked mental retardation (MRX) to an approximately 3-Mb region between DXS31 and STS, the precise location has not been determined. In this paper, we describe a 14 7/12 year old Japanese boy with mental retardation and an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1, and compare the deletion map with that of previously reported three familial male patients with low-normal intelligence and a similar interstitial deletion at Xp22.3. The results suggest that the MRX gene is further localized to the roughly 1.5-Mb region between DXS1060 and DXS1139.
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PMID:Mental retardation in a boy with an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1: implication for the MRX locus. 1034 Jun 59

The gene responsible for nonsyndromic mental retardation in a family with 7 affected males has been localized to Xp21. The maximal two-point lod score was 3.31 for tight linkage to marker DXS1202 in Xp21.3-p22.3 with crossovers between the 3' portion of the DMD gene (DXS1234) proximally and locus DXS989 distally. The XLMR gene in this family has been assigned the designation MRX29. The localization overlaps with at least six other MRX entities linked to the distal short arm of the X chromosome.
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PMID:Nonsyndromic X-linked mental retardation: review and mapping of MRX29 to Xp21. 900 95

A large family (MRX48) with a nonspecific X-linked mental retardation condition is described. An X-linked semidominant inheritance is suggested by the segregation in three generations of a moderate to severe mental retardation in seven males and by a milder intellectual impairment in two females, without any specific clinical, radiological, or biological feature. Two-point linkage analysis demonstrated significant linkage between the disorder and several markers in Xq28 (maximum LOD score [Zmax] = 2.71 at recombination fraction [theta] = 0); multipoint linkage analyses confirmed the significant linkage with a Zmax of 3.3 at theta = 0, at DXS1684. A recombination event observed with the flanking marker DXS8011 delineates a locus between this marker and the telomere. The approximate length of this locus is 8-9 cM, corresponding to 5.5-6 Mb. In an attempt to explain the variable intellectual impairment in females, we examined X-chromosome inactivation in all females of the family. Inactivation patterns in lymphocytes were random or moderately skewed, and no correlation between the phenotypic status and a specific inactivation pattern was observed. The interval of assignment noted in this family overlaps with five MRX loci previously reported in Xq28.
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PMID:A gene for dominant nonspecific X-linked mental retardation is located in Xq28. 910 37

We describe a large family with nonspecific X-linked mental retardation (MRX 47). An X-linked recessive transmission is suggested by the inheritance from the mothers in two generations of a moderate to severe form of mental retardation in six males, without any specific clinical findings. Two point linkage analysis demonstrated significant linkage between the disorder and two markers in Xq23 (Zmax = 3.75, theta = 0). Multipoint linkage analyses confirmed the significant linkage with a maximum lod score (Z = 3.96, theta = 0) at DXS1059. Recombination events observed with the flanking markers DXS1105 and DXS8067 delineate a 17 cM interval. This interval overlaps with several loci of XLMR disorders previously localized in Xq23-q24, which are reviewed herein.
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PMID:Gene for nonspecific X-linked mental retardation (MRX 47) is located in Xq22.3-q24. 933 63

We report on a patient with a pericentric inversion of the X chromosome, 46,Y,inv(X) (p11.2q21.3), who was referred for cytogenetic analysis because of mild mental retardation, short stature, prepubescent macro-orchidism, and submucous cleft palate. The same chromosomal abnormality was found in the proband's mother. The inverted X chromosome was late replicating in all the mother's lymphocytes studied, indicative of a likely unbalanced inversion. We show, by fluorescence in situ hybridisation (FISH) using a panel of ordered yeast artificial chromosome (YAC) clones, that the Xp breakpoint is localised in Xp11.23 between DXS146 and DXS255 and that the Xq breakpoint is assigned to the X-Y homologous region in Xq21.3. YACs crossing the Xp and Xq breakpoints have been identified. One of these two breakpoints could be linked to the mental retardation in this patient as many non-specific mental retardation (MRX) loci have previously been located in the pericentromeric region of the X chromosome. Morever, the elucidation at the molecular level of this rearrangement will also indicate if cleft palate or prepubescent macro-orchidism, or both, in this boy are related to one of the two X breakpoints.
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PMID:Characterisation of an inverted X chromosome (p11.2q21.3) associated with mental retardation using FISH. 950 95

Primary or nonspecific X-linked mental retardation (MRX) is a heterogeneous condition in which affected patients do not have any distinctive clinical or biochemical features in common apart from cognitive impairment. Although it is present in approximately 0.15-0.3% of males, most of the genetic defects associated with MRX, which may involve more than ten different genes, remain unknown. Here we report the characterization of a new gene on the long arm of the X-chromosome (position Xq12) and the identification in unrelated individuals of different mutations that are predicted to cause a loss of function. This gene is highly expressed in fetal brain and encodes a protein of relative molecular mass 91K, named oligophrenin-1, which contains a domain typical of a Rho-GTPase-activating protein (rhoGAP). By enhancing their GTPase activity, GAP proteins inactivate small Rho and Ras proteins, so inactivation of rhoGAP proteins might cause constitutive activation of their GTPase targets. Such activation is known to affect cell migration and outgrowth of axons and dendrites in vivo. Our results demonstrate an association between cognitive impairment and a defect in a signalling pathway that depends on a Ras-like GTPase.
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PMID:Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. 958 72

A new family with a non-specific X-linked mental retardation (MRX55) is described. An X-linked recessive inheritance is suggested by the segregation from two healthy transmitting females of moderate mental retardation in three males, without any specific clinical, radiological or biological features. Two point linkage analysis demonstrated significant linkage between the disorder and several markers in Xp11 (Zmax = 2.11, theta = 0); multipoint linkage analyses confirmed the significant linkage with a maximum lod score (Z = 2.11 at theta = 0, at DXS8012). Recombination events observed with the flanking markers DXS1068 and DXS1275 delineate a 34 centimorgan interval in the pericentromeric region. The interval of assignment pointed out in this family overlaps with several MRX loci previously reported in Xp11 which are reviewed here in.
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PMID:A gene for non-specific X-linked mental retardation (MRX55) is located in Xp11. 959 45

Non-specific X-linked mental retardation (MRX) is a very common disorder which affects approximately 1 in 600 males. Despite this high frequency, little is known about the molecular defects underlying this disorder, mainly because of the clinical and genetic heterogeneity which is evident from linkage studies. Recently, a collaborative study using the candidate gene approach demonstrated the presence of mutations in GDIalpha, a Rab GDP-dissociation inhibitor encoded by a gene localized in Xq28, associated with non-specific mental retardation. GDIalpha is mainly a brain-specific protein that plays a critical role in the recycling of Rab GTPases involved in membrane vesicular transport. The study presented here was designed to assess the prevalence of mutations in the GDIalpha in mentally retarded patients and to discuss the clinical phenotypes observed in affected individuals. Mutation screening of the whole coding region of the GDIalpha gene, using a combination of denaturing gradient gel electrophoresis and direct sequencing, was carried out in 164 patients found negative for expansions across the FRAXA GCC repeat. In addition to the nonsense mutation recently reported in MRX48, we have identified a novel missense mutation in exon 11 of the GDIalpha gene in one familial form of non-specific mental retardation. In this family (family R), all affected males show moderate to severe mental retardation, and the X-linked semidominant inheritance is strongly suggested by the severe phenotypes in males with respect to mildly affected females or unaffected obligatory carriers. This study showed that the prevalence of GDIalpha mutations in non-specific mental retardation could be estimated to be 0.5-1%, and molecular diagnosis and genetic counselling in some cases of non-specific mental handicap can now be provided.
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PMID:Non-specific X-linked semidominant mental retardation by mutations in a Rab GDP-dissociation inhibitor. 966 74


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