Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder resulting in progressive degeneration of the muscle. It affects about 1 in 3,500 male children. Becker's muscular dystrophy is a less severe disease allelic to DMD. Some 30% of DMD patients suffer from various degrees of mental retardation. The giant DMD gene spans about 2,000 kilobases and codes for a 14-kilobase messenger RNA and a protein of molecular weight 427,000. DMD mRNA is most abundant in skeletal and cardiac muscle and less so in smooth muscle. We reported that the expression of the gene is developmentally regulated during the differentiation of primary muscle cultures and in myogenic cell lines in a way similar to the expression of muscle-specific genes such as myosin light chain 2 and skeletal muscle actin. Similar results have been obtained with human primary myogenic cells. Significant levels of DMD mRNA are found in brain tissue. Here we show that the transcript of the DMD gene and the amino terminal of the encoded protein differ in brain and muscle. The 5' ends of these mRNA species are derived from different exons. The results suggest that the two mRNA types are transcribed from different promoters.
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PMID:Duchenne muscular dystrophy gene product is not identical in muscle and brain. 290 92

Of the approximately 170 families with X-linked muscular dystrophy of the Duchenne (DMD) and Becker (BMD) type in Finland, we have studied 90 unrelated patients for intragenic deletions by using the cDNA probes described by Koenig et al. Forty-five patients (50%) had molecular deletions of one or several of the 65 exon-containing HindIII fragments. In six deletion cases junction fragments of altered size were seen. Thirty-eight (84%) of the 45 deletions were detected using only two (1-2a and 8) of the six cDNA subclones. Using a wheelchair age of 12 years to distinguish between DMD and BMD, we found that the proportions of patients with deletions were similar. Deletions were equally common in familial and sporadic disease. BMD was more commonly caused by deletions in the 5' end of the gene than was DMD. In at least three instances deletions of similar type resulted in diseases of similar severity. Of 14 patients with mental retardation seven had deletions; six of these comprised exons contained in probe 8. We conclude that cDNA hybridization studies provide a powerful diagnostic tool in DMD and BMD and that they promise to produce better insights into molecular-clinical correlations.
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PMID:Gene deletions in X-linked muscular dystrophy. 292 94

A syndrome of Duchenne muscular dystrophy (DMD), adrenal hypoplasia, glycerol kinase deficiency, and mental retardation has been recognised. We report a further case ascertained from a history of DMD, severe mental retardation, and an Addison-like disorder. Cytogenetic analysis of the proband revealed an interstitial deletion of the short arm of the X chromosome. from Xp21.1 to Xp22.11, comprising about 9% of the length of the normal X chromosome. His mother was heterozygous for the deletion, but his maternal grandmother and sister both had two normal X chromosomes. DNA probe analysis confirmed the existence of a deletion in the affected boy, as probes 754, C7, XJ1-1, and pERT87 consistently failed to hybridize to his DNA. His sister was heterozygous for the RFLP associated with 754, thus confirming that she had two normal X chromosomes. There was no evidence of chronic granulomatous disease, other immunological defect, or retinitis pigmentosa in this case. Biochemical studies revealed gross glyceroluria and hyperglycerolaemia, indicating glycerol kinase deficiency which has been confirmed enzymatically. We have subsequently screened 21 other boys with DMD for glyceroluria and found one other case. Cytogenetic analysis has also been performed in nine other families, where a boy with DMD has been shown to have a deletion of DNA sequences localised to the region Xp21. None of these cases demonstrated any cytogenetic abnormality, nor has their clinical course been unusual.
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PMID:Duchenne muscular dystrophy with adrenal insufficiency and glycerol kinase deficiency: high resolution cytogenetic analysis with molecular, biochemical, and clinical studies. 302 43

Epidemiological studies have suggested that non-specific X-linked mental retardation (XLMR) might be at least as frequent as the fragile X syndrome. The identification of all mutations causing XLMR would thus appear of prime importance. In the absence of other clinical signs the problem of genetic heterogeneity is acute. This can be partly overcome by the analysis of large families. We have been able to perform linkage analysis in 3 such families. The condition in family 1 was described as clinically resembling the fra (X) syndrome by Proops et al [1983]: the kindred includes 7 affected males in 3 sibships. Family 2 from Denmark has affected males in 4 generations; however, several affected relatives in this extended pedigree are deceased. Family 3 from France counts 6 affected males in two sibships. The families were analysed with about 25 X-linked markers. Linkage with markers in Xp22.2-p22.3 was found in family 1: z(theta) = 2.62 at theta = 0.06 for DXS85 (probe 782). Suggestion of linkage was found in family 2 with both the Duchenne muscular dystrophy region (DXS164 in Xp21.2) and with DXS1 (Xq11-q12). In family 3, DXS159 (Xq12-q13) gave a lod score of 2.53 at theta = 0; results were compatible with localisation of the putative XLMR locus in this family proximal to DXYS1 (Xq21). These data suggest that at least two non-specific XLMR loci could exist, one in Xp22 and the other in the q12-q13 region.
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PMID:Linkage analysis suggests at least two loci for X-linked non-specific mental retardation. 317 65

Duchenne muscular dystrophy (DMD) is one of the most serious neuromuscular afflictions in childhood. The present analysis describes clinical, genetic and epidemiological features in a total of 675 DMD cases, 666 males and 9 females, reported from 20 national hospitals for muscle diseases in Japan. The results are as follows: 1) Average ages of milestones of progression were: onset at 3.6 +/- 1.7, Gower's sign 5.2 +/- 2.3, inability to walk 9.8 +/- 2.1, death 19.5 +/- 3.6 years old, respectively. The patients died 10.9 +/- 3.3 years after the age of inability to walk. 2) Proportion of selected abnormalities (knee contracture, ankle contracture, kyphoscoliosis) and abnormal findings in electrocardiograms increased with age, whereas pseudohypertrophy of the calves, abnormal findings of electromyograms, and mental retardation remained constant. 83-95% of patients were unable to turn the body in bed over 20 years old. 3) Survival rates at 20 and 27 years old were 63%, and 35%, respectively. The 50% survival rate was observed in 22-23 years of age. 4) The proportion of the sporadic cases was compatible with 1/3, as expected for on X-linked lethal trait assuming complete penetrance. 5) The incidence rate and prevalence rate among males were estimated to be 29.2 x 10(-5) and 6. 7 x 10(-5), respectively. The estimated mutation rates in egg and sperm were 9.2 x -5 and 10.9 x 10(-5)/gamete/generation, respectively.
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PMID:[Genetic epidemiology of Duchenne muscular dystrophy in Japan]. 324 68

Molecular genetics has transformed clinical concepts of Duchenne muscular dystrophy (DMD) in several different ways. (1) The disease can now be defined as a myopathy due to mutation at Xp21, a specific locus on the short arm of the X chromosome. (2) As a consequence of that discovery, any myopathy due to mutation at Xp21 should be a variant of DMD and should affect the same gene product. Moreover, any myopathy due to mutation at a location other than Xp21 should affect some other gene product. (3) For these reasons, DNA analysis is now needed for clinical diagnosis of muscle disease. (4) Xp21 myopathies may be mild or severe, may occur in females even though X-linked, and may be manifest only by high serum levels of creatine kinase. (5) Mental retardation is not consistently related to diseases that are encoded at Xp21. The association of mental retardation with DMD may be due to mutation in a separate gene near that for DMD. Concepts may soon be altered again as we learn about the affected gene product (dystrophin) and its role in these diseases.
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PMID:Clinical concepts of Duchenne muscular dystrophy. The impact of molecular genetics. 328 82

Duchenne muscular dystrophy (DMD), a sex-linked degenerative disorder of the muscle, is one of the most common lethal genetic diseases in man. It affects about one male in 3,500, with an estimated one-third of cases being caused by new mutations. A less severe disease, Becker's muscular dystrophy (BMD), maps to the same chromosomal locus and is most probably an allelic form of DMD. Both diseases are sometimes associated with various degrees of mental retardation; the molecular basis of these phenotypes is unknown (for review, see ref. 1). The giant DMD gene spans approximately 2,000 kilobases (kb) (0.05% of the human genome) and encodes a 14-kb mRNA. The tissue-specificity of its expression has not been precisely determined. Monaco et al., using Northern blots, reported expression of the gene in human fetal skeletal muscle and small intestine but not in human fetal brain, or in human cultured myoblasts and transformed B and T cells. More recently, expression was detected in mouse skeletal and cardiac muscle, but not in mouse brain. Here we show, using a ribonuclease protection assay, that the DMD gene is developmentally regulated in rat and mouse myogenic cell cultures, and that it is expressed in rat and mouse striated muscle, in mouse smooth muscle and in rat, mouse and rabbit brain. We could not detect transcripts in other non-muscle tissues.
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PMID:Expression of the putative Duchenne muscular dystrophy gene in differentiated myogenic cell cultures and in the brain. 334 Feb 14

Complementary DNA clones were isolated that represent the 5' terminal 2.5 kilobases of the murine Duchenne muscular dystrophy (Dmd) messenger RNA (mRNA). Mouse Dmd mRNA was detectable in skeletal and cardiac muscle and at a level approximately 90 percent lower in brain. Dmd mRNA is also present, but at much lower than normal levels, in both the muscle and brain of three different strains of dystrophic mdx mice. The identification of Dmd mRNA in brain raises the possibility of a relation between human Duchenne muscular dystrophy (DMD) gene expression and the mental retardation found in some DMD males. These results also provide evidence that the mdx mutations are allelic variants of mouse Dmd gene mutations.
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PMID:Expression of the murine Duchenne muscular dystrophy gene in muscle and brain. 334 39

The preliminary results of a study to investigate possible genetic heterogeneity in Duchenne muscular dystrophy (DMD) are reported. Ninety-eight patients have been analyzed: 47 were isolated cases; 51 were familial cases. The patients were divided into three groups (normal intelligence, borderline, and mentally retarded) according to mental capacity and a comparison of clinical evolution (onset of clinical signs and loss of ambulation) as well as serum enzyme activities (creatine-kinase and pyruvate-kinase). In addition intrafamilial correlation analysis was done for the same parameters. The preliminary results did not show a significant difference between DMD patients with normal intelligence and those with mental retardation.
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PMID:Investigation on genetic heterogeneity in Duchenne muscular dystrophy. 370 99

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.
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PMID:Duchenne-like muscular dystrophy in two sisters with normal karyotypes: evidence for autosomal recessive inheritance. 404 97


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