Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two sisters, products of a consanguineous marriage (with a total of 12 children) showed muscle weakness at ages 7 and 6 yrs, respectively. The symptoms progressed rapidly and the patients were confined to wheelchairs at ages of 12 and 11 yrs, respectively. They had mild facial weakness and pseudohypertrophy of the calves, but neither cardiomyopathy nor mental retardation. Serum CK activities exceeded upper normal limit by 70 to 85-fold. Muscle biopsies were compatible with muscular dystrophy. Both girls had a normal karyotype. The healthy mother had mild CK elevations in two out of three occasions, but the muscle biopsy was normal. Three out of the six unaffected sibs had mild CK elevations. The findings support the concept of severe progressive muscular dystrophy with autosomal recessive inheritance. The condition is clinically indistinguishable from Duchenne muscular dystrophy.
 ...
PMID:Duchenne-like muscular dystrophy in two sisters with normal karyotypes: evidence for autosomal recessive inheritance. 404 97

A balanced de novo (X;9) translocation was observed in a patient with progressive muscular dystrophy of Duchenne's type (DMD), Turner's syndrome, epilepsy and mental retardation. The involvement of the paternal X is suggested. The assignment of the gene locus for DMD is confirmed on Xp21.
 ...
PMID:Turner's syndrome and Duchenne muscular dystrophy in a girl with an X; autosome translocation. 633 82

An epidemiological study was carried out on the group of moderately retarded brothers (IQ, 30-55) identified by Turner and Turner [1974]. Of the original 58 sets of brothers, 54 sets (now 17 to 32 years old) were traced; another four sets (missed in the earlier survey) were added. Forty-five of the 58 pairs were diagnosed as having nonspecific X-linked mental retardation (MR) giving an overall frequency of 5.57 moderately retarded males/10,000 male births. In 12 of the 45 families, affected males had the fragile(X) and macroorchidism; six had macroorchidism alone, giving a frequency of 2.8 moderately retarded males with X-linked MR and macroorchidism +/- the fragile(X) per 10,000 males. Corresponding heterozygote frequencies are 7.34 and 3.65/10,000 females respectively. A new subgrouping of nonspecific X-linked mental retardation is described in six families: X-linked MR, macroorchidism without the fragile(X). Three other X-linked conditions were identified: in one family, the Coffin-Lowry syndrome, in another, Duchenne muscular dystrophy, and in two families X-linked MR and muscle atrophy. Half (56%) of the obligatory carriers of fra(X)-MR in this study were dull to mildly retarded. The mildly retarded heterozygotes had a significantly higher percentage of fra(X) expressing lymphocytes as compared to the intellectually normal heterozygotes. When the three types of nonspecific X-linked MR for which population frequencies were calculated were considered together, half of the obligatory carriers (46%) were dull or mildly retarded, thus confirming that this condition is a significant cause of mild intellectual handicap in females.
 ...
PMID:The diagnosis and frequency of X-linked conditions in a cohort of moderately retarded males with affected brothers. 668 25

The fragile X-mental retardation syndrome is defined by a moderate to severe mental retardation associated with a cytogenetic marker, a fragile site localized on the long arm of the X chromosome at band Xq 27. This syndrome has recently been recognized as one of the major causes of genetically determined mental retardation, and as one of the most important X-linked diseases with respect to its frequency (analogous to that of Duchenne muscular dystrophy or of haemophilia A) and severity. In the absence of treatment, genetic screening for this disease would seem particularly important. Prenatal diagnosis is now feasible although difficult and detection of heterozygous carriers is only possible in approximately 50% of cases. The recent demonstration of genetic linkage between the glucose 6-phosphate dehydrogenase (G6PD)-colour blindness cluster (at Xq28) and the fragile X locus has suggested that the fragile site is indeed the site of the mutation. We show here that the fragile X and haemophilia B loci are closely linked, using as genetic marker a polymorphism of the coagulation factor IX gene. Our study of a large family has demonstrated transmission through a phenotypically normal male, a feature previously described in retrospective analysis of a few other fragile X pedigrees. Restriction polymorphisms associated with the factor IX gene should be useful for analysing this peculiar aspect of the genetics of the fragile X syndrome, and for genetic screening of the disease.
 ...
PMID:Close linkage of fragile X-mental retardation syndrome to haemophilia B and transmission through a normal male. 668 1

Recent psychological testing and neuropathologic studies support the occurrence of relative retardation, an in some cases severe retardation, in patients with Duchenne muscular dystrophy. Muscle deterioration and wasting are associated with the natural progression of the disease. Progressive physical weakness can be described in the following stages: early, walking, wheelchair, and late. The more emotionally mature the family, the more effective they are in coping at each stage of the disease. Nevertheless, a constant stress is present in all families. This stress can increase or plateau at the various stages and as new problems are encountered. When mental retardation is significant, the stress on the family become even more marked.
 ...
PMID:Challenges in the care of the retarded child with Duchenne muscular dystrophy. 720 93

Duchenne muscular dystrophy is associated with mental retardation and several dystrophin transcripts are differentially expressed in specific brain areas. G-dystrophin (Dp71) is known to be the predominant isoform in the brain. We have localized its mRNA to be present predominantly in the dentate gyrus and in the olfactory bulb. This distribution is specific and significantly different from that for the full-size dystrophin transcripts, present mainly in CA regions of the hippocampus, in the cerebral cortex and in cerebellar Purkinje cells. Furthermore, our data show that the various dystrophins co-localize with the dystroglycan in the brain.
 ...
PMID:Specific expression of G-dystrophin (Dp71) in the brain. 761 78

Duchenne muscular dystrophy (DMD) is one of a range of muscular dystrophies caused by abnormalities of the short arm of the X chromosome (Xp21), which often cause mental retardation in addition to progressive muscular weakness. Normal dystrophin expression is lacking in both skeletal muscle and brain of affected subjects. Phosphorus-31 magnetic resonance spectroscopy has shown several abnormalities in skeletal muscle in DMD. We looked for similar abnormalities in brain in patients with DMD and related the findings to neuropsychological test results. We studied by magnetic resonance spectroscopy 19 boys (aged 76-167 months) diagnosed as having DMD and 19 control boys of similar age (87-135 months). Intelligence quotient (IQ) was assessed with the Wechsler Intelligence Scale for children. The DMD patients had significantly higher values than the controls in the brain ratios of inorganic phosphate to adenosine triphosphate (mean 0.53 [SD 0.21] vs 0.36 [0.09], p = 0.003), to phosphomonoesters (0.40 [0.07] vs 0.29 [0.07], p = 0.0001), and to phosphocreatine (0.44 [0.10] vs 0.37 [0.08], p = 0.02). There were significant differences between the DMD patients and the controls in full-scale IQ (76 [16] vs 101 [16], p = 0.0001), performance IQ (78 [17] vs 94 [14], p = 0.003), and verbal IQ (78 [17] vs 106 [17], p = 0.0001). These altered metabolite ratios parallel the findings in dystrophic muscle and suggest bioenergetic similarities in tissues that lack dystrophin.
 ...
PMID:Brain abnormalities in Duchenne muscular dystrophy: phosphorus-31 magnetic resonance spectroscopy and neuropsychological study. 774 55

Duchenne muscular dystrophy (DMD) is accompanied by varying degrees of mental retardation. The molecular basis for this is unknown, although at least four dystrophin transcripts regulated by specific promoters and undergoing elaborate splicing control are present in brain areas associated with cognitive function. In muscle the absence of dystrophin causes instability of a dystrophin-associated protein complex (DAPC) linking the cytoskeleton to the extracellular matrix; this disruption is accompanied by muscle necrosis. The laminin-binding component of DAPC, dystroglycan, in contrast to other components of DAPC, has been found in brain homogenates. This suggests that the link between the membrane cytoskeleton and extracellular matrix mediated by dystrophin-dystroglycan may play a functional role in brain. We have cloned a mouse dystroglycan partial cDNA and have mapped this gene in the mouse to chromosome 9. Further, in situ hybridisation to mouse brain sections shows that the dystroglycan gene is expressed in relatively few structures and co-localises with dystrophin mRNA in hippocampus, dentate gyrus, olfactory bulb and Purkinje neurons but, surprisingly, not in the cortex. Dystroglycan is also expressed in those brain areas where the dystrophin-related protein (utrophin) is present. Our results provide a basis for a future characterisation of the role of dystrophin-dystroglycan association in the brain.
 ...
PMID:Dystroglycan: brain localisation and chromosome mapping in the mouse. 783 16

The authors collected Verbal, Performance and Full-scale IQs for 74 patients in whom complete analysis of the dystrophin gene for deletions and duplications had been performed. There was a significant difference in the mean Full-scale IQ between patients with deletions at the 5' and 3' ends of the gene, with no patients with 5' deletions having mental retardation. No relationship was established between mental retardation and the presence or absence of deletions or length of deletions, and similar deletions were observed in the presence and absence of mental retardation. Although distal deletions were more commonly associated with mental retardation, there was no clear evidence for a particular region of the dystrophin gene being specifically responsible for IQ. The intellectual deficit seen in DMD may be a consequence of cerebral hypoxia, ue to malfunction of smooth muscle dystrophin.
 ...
PMID:Deletion status and intellectual impairment in Duchenne muscular dystrophy. 789 Jan 31

We have previously reported linkage analysis in 3 families with non-specific X-linked mental retardation (XLMR). This used RFLPs and was limited by the relatively low informativeness and density of markers available. We have performed a new linkage analysis using microsatellites (including new Genethon markers) in the two most informative families. In the MRX2 family, a lod score of 2.61 at theta = 0.05 had previously been obtained with DXS85 in Xp22.2. We now report a tighter linkage with AFM 135xe7 (DXS989, z = 4.62 at theta = 0.00) and established the order DXS85-DXS207-DXS999 (AFM234 y12)-MRX2, DXS365, DXS1052 (AFM 163yh2), DXS989-DXS1065 (AFM224zf2), DMD 3'. The localization of MRX2 in Xp22.2-p22.1 is thus clearly different from the more distal MRX gene defined by patients with contiguous gene syndromes. In the MRX4 family, a maximum lod score of 2.53 at theta = 0.00 had been obtained with DXS159 in Xq13. Our present study did not show recombination from ALAS2 in Xp11.21 to DXS441 in Xq13.3 (z = 3.38 at theta = 0.00 for the latter marker) and the closest flanking markers are DXS255 in Xp11.22 and DXYS1 in Xq21.3. Reduced recombination around the centromere prevents precise mapping. The localisation of MRX4 overlaps with that of several other MRX families.
 ...
PMID:Non-specific X-linked mental retardation: linkage analysis in MRX2 and MRX4 families revisited. 794 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>