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 (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

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

A genetic linkage study was performed on a large four-generation family with variable nonspecific X-linked mental retardation (MRX16), speech abnormalities, and retardation of all milestones. Significant linkage was found in the Xq28 region with loci DXS52, DXS15, BGN, and DXS1108 with maximum LOD scores of 4.86, 4.01, 4.83, and 5.43, respectively, at theta = 0.00. Recombination was observed at the locus DXS1113, thus mapping the gene in an 8-Mb interval between this marker and the Xq telomere. Linkage intervals of three other MRX families overlap with this interval in Xq28 where the RABGDIA gene, mutated in the MRX41 and MRX48 families, is also located. In MRX3, MRX28, but also in MRX16, no alteration of RABGDIA has been found, thus suggesting the existence of at least two MRX genes in distal Xq28.
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PMID:X-linked nonspecific mental retardation (MRX16) mapping to distal Xq28: linkage study and neuropsychological data in a large family. 1023 54