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)

The P-20 intragenic marker was used to test for restriction fragment length polymorphisms in unrelated Chinese patients with Duchenne or Becker muscular dystrophy or X-linked mental retardation. In addition to polymorphism at the 6.0/3.5 kb MspI allelic site, we found an independent and high frequency of polymorphism at the 2.2/1.8 kb site. This differs from results found with other populations.
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PMID:Significantly higher frequency of the MspI 2.2 kb allele of the Duchenne muscular dystrophy intragenic probe P-20 in the Chinese population. 138 93

We report the results of screening for molecular deletions in 164 boys with DMD and BMD and correlation of deletions with clinical features. A deletion was detected in 100 cases (61%) by Southern blot hybridization analysis with cDNA probes. Thirty-eight different deletions and two duplications were identified. All deletions except one (deletion of exons 48-53) found in males with DMD disrupted the translational reading frame of the gene; however, six deletions in boys with BMD were out of frame. The same deletion in different individuals was found to occur with or without mental impairment, and many different deletions were associated with mental retardation. We were able to ascertain a series of boys [from this study and a previous one (Hodgson S V, Hart K, Abbs S, et al. Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy. J Med Genet 1989; 26: 682-693)] without significant mental retardation who had deletions which, when combined, covered the whole region of the gene in which deletions are commonly found, and within which region individual deletions can be associated with mental retardation.
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PMID:Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy, with special reference to mental ability. 148 53

Dystrophin, the protein product of the Duchenne muscular dystrophy gene, is expressed in brain as well as muscle. The role of dystrophin in the brain is not clear, though one-third of Duchenne muscular dystrophy patients exhibit some degree of mental retardation. We have isolated the genomic region encoding the alternative 5' terminus of dystrophin used in the brain. Primer extension and polymerase chain reaction assays on RNA demonstrate that this region contains an alternative promoter for dystrophin used in the brain. Physical mapping of this region indicates that this brain promoter is located greater than 90 kilobases 5' to the promoter used in muscle and 400 kilobases from exon 2 to which it is spliced. The large physical distance between the promoters, taken together with their known tissue selectivities, suggests that in certain patients a deletion of either dystrophin promoter might give rise to reduced dystrophin expression selective to brain or muscle. We have identified one such individual with specific deletion of the dystrophin muscle promoter, giving rise to Becker muscular dystrophy, and we predict that specific loss of the brain promoter may be one cause of X chromosome-linked mental retardation.
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PMID:Dystrophin is transcribed in brain from a distant upstream promoter. 199 28

Cloned cDNA sequences representing exons from the Duchenne/Becker muscular dystrophy (DMD/BMD) gene were used for deletion screening in a population of 287 males males affected with DMD or BMD. The clinical phenotypes of affected boys were classified into three clinical severity groups based on the age at which ambulation was lost. Boys in group 1 had DMD, losing ambulation before their 13th birthday; those in group 2 had disease of intermediate severity, losing ambulation between the ages of 13 and 16 years; and boys in group 3 had BMD, being ambulant beyond 16 years. A fourth group consisted of patients too young to be classified. Clinical group allocation was made without previous knowledge of the DNA results. A gene deletion was found in 124 cases where the clinical severity group of the affected boy was known. The extent of the deletions was delineated using cDNA probes. There were 74 different deletions. Fifty-five of these were unique to individual patients, but the other 19 were found in at least two unrelated patients. The different clinical groups showed generally similar distributions of deletions, and the number of exon bands deleted (that is, deletion size) was independent of phenotype. Some specific deletion types, however, correlated with the clinical severity of the disease. Deletion of exons containing HindIII fragments 33 and 34 and 33 to 35 were associated with BMD and were not found in patients with DMD. Deletions 3 to 7 occurred in four patients with the intermediate phenotype and one patient with BMD. Other shared deletions were associated with DMD, although in four cases patients with disease of intermediate severity apparently shared the same deletion with boys with DMD. The range of phenotypes observed, and the overlap at the genetic level between severe and intermediate and mild and intermediate forms of dystrophy, emphasizes the essential continuity of the clinical spectrum of DMD/BMD. There were no characteristic deletions found in boys with mental retardation or short stature which differed from deletions in affected boys without these features.
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PMID:Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy. 258 68

We have studied 30 French patients with X-linked muscular dystrophy of the Duchenne (DMD) and Becker (BMD) types for intragenic deletions, using the cDNA probes of the DMD/BMD gene. Sixteen patients (53%) had molecular deletions in one or several of the 65 Hind III fragments containing exons detected with the DNA probes; in four deletion cases junction, fragments of altered size were seen. Fourteen (87%) of the deletions were detected using only two (1-2a and 8) and fifteen with 8+(2b-3) of the cDNA subclones. In our limited sample, BMD was caused by deletions in the 5' end of the gene, and in two instances of DMD, deletions of similar types resulted in diseases of similar severity. Of two patients with mental retardation, both had deletions comprised exons contained in probe 8, but other patients without mental retardation are also deleted with probe 8. We conclude that cDNA hybridization studies provide a powerful diagnostic tool in DMD and BMD families.
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PMID:Molecular deletion patterns in Duchenne muscular dystrophy patients. 261 Apr 87

In the seven years since the first human gene was cloned, several hundred coding sequences and many more random single copy DNA sequences have been isolated. Many of these show restriction fragment length polymorphisms (RFLPs) and can be used as genetic markers in inheritance studies. RFLPs enable the construction of complete linkage maps of individual human chromosomes which can then be used as a mapping resource for other genes and disease loci. The isolation of chromosome specific sequences has been greatly facilitated by the purification of human chromosomes by flow cytometry. Sub-localisation of the polymorphic DNA probes along the chromosome can be achieved using in situ hybridisation or rodent/human hybrid cell lines. There are now more than one hundred DNA probes assigned to the human X chromosome and a preliminary genetic map suggests that the chromosome is at least 200 cm long. Some of these DNA sequences have been shown to be linked to disease loci such as Duchenne and Becker muscular dystrophy, X-linked mental retardation and retinitis pigmentosa.
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PMID:Towards a complete linkage map of the human X chromosome. 287 29

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

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

There are some indications that Becker muscular dystrophy (BMD) might be related to mental disorders and mental retardation (MR). To investigate this question, we made a standardized psychiatric and intellectual level assessment of 22 BMD patients in comparison with 22 limb-girdle muscular dystrophy (LGMD) patients. There were not significant differences between the two groups. Twelve patients (54.5%) in each group received at least one lifetime psychiatric diagnosis, the most frequent being depressive disorders. The intelligence quotient means for BMD was 85.9 and 87.8 for LGMD. There was one case of mild MR among BMD patients and two cases among LGMD patients.
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PMID:Becker and limb-girdle muscular dystrophies: a psychiatric and intellectual level comparative study. 748 32


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