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)

We report four patients, currently aged 15, 17, 19, and 42 years, with X-linked dystrophinopathy who presented with mental retardation (IQ range, 60-68) and psychiatric disturbance in the absence of muscle weakness. All patients had elevated serum creatine kinase and dystrophic changes on muscle biopsy. There were alterations in the size and abundance of dystrophin on immunohistochemistry and immunoblotting in all cases, consistent with a molecular diagnosis of Becker's muscular dystrophy. Two patients had deletions of the dystrophin gene on DNA analysis. These findings suggest that Becker's muscular dystrophy may be associated with a predominantly neuropsychiatric presentation and that dystrophinopathy should be considered in the differential diagnosis of unexplained cognitive or psychiatric disturbance in males. Serum creatine kinase may provide an adequate screening test in this clinical situation.
 ...
PMID:Cognitive dysfunction as the major presenting feature of Becker's muscular dystrophy. 861 13

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder primarily affecting young boys, often causing mental retardation in addition to the well-known progressive muscular weakness. Normal dystrophin expression is lacking in skeletal muscle and the CNS of both DMD children and the mdx mouse model. To date, 31P-magnetic resonance spectroscopy (MRS) has shown in vivo several abnormalities within skeletal muscle of mdx mice and DMD boys. In this study, we determined whether similar abnormalities occur in mdx brain in vivo by using 31P-MRS in addition to metabolite and enzyme analysis to study cerebral metabolism. An increased inorganic phosphate (P(i))/phosphocreatine (PCr) and pH was found in vivo for mdx brain compared with controls, and biochemical analysis showed a reduction in total creatine, an increased extracellular and decreased intracellular volume in mdx brain. No differences were found in any glycolytic or mitochondrial maximal enzyme activities. These changes are discussed with respect to the biochemical changes found in muscle from DMD patients and mdx mice. It is proposed that these biochemical changes may be a factor in the reduced cognitive capacity of mdx mice and some DMD children.
 ...
PMID:Brain metabolism is abnormal in the mdx model of Duchenne muscular dystrophy. 867 81

We have reported adhalin gene mutations in 4 patients from 3 families with malignant limb-girdle muscular dystrophy (MLGMD), and summarized the clinical features in adhalin-deficient muscular dystrophy (ADMD) reported as severe childhood autosomal recessive muscular dystrophy (SCARMD) in the English literatures. Adhalin cDNA amplified from RNA by reverse transcription polymerase chain reaction (RT-PCR) was sequenced in 3 patients from 2 consanguinous families (Wa. and Ta.) with MLGMD who showed immunohistochemically a complete deficiency of adhalin in the skeletal muscle, and adhalin genomic DNA amplified by PCR was sequenced in 1 patient from a non-consanguinous family (Ma.). In one patient from family Wa., a cytosine to thymine substitution at nt. 229 was identified in the adhalin gene, resulting in the replacement of Arg by Cys at codon 77. In two patients from family Ta., an adenine to guanine substitution at nt. 410 and an insertion of 15 bases between nt. 408 and 409 were identified, resulting in Glu to Gly replacement at codon 137 and insertion of a peptide with 5 amino acids. In one patient from family Ma., a deletion of adenine at nt. 404 or nt. 405 and a thymidine to cytosine substitution at nt. 470 were identified. These amino acid replacements are expected to change the secondary and tertiary structure, which may affect the interaction of adhalin with other dystrophin-associated glycoproteins and basal lamina, and may subsequently cause the degeneration of muscle fibers. Sixty-six cases from 49 families with ADMD have been reported in the literature. Compared with patients with Duchenne muscular dystrophy (DMD), patients with ADMD were older in age at the time of onset or loss of ambulation. Mental retardation and cardiac dysfunction were rarely observed in ADMD patients. On muscle histology, the number of necrotic fibers, opaque fibers and regenerative fibers was less in ADMD. ADMD was classified into two groups; complete and incomplete adhalin-deficient. There was no essential difference between the two groups in clinical features and muscle histology, but the former was characterized by more severe clinical features than the latter. ADMD can be caused by various types of mutations in the adhalin gene.
 ...
PMID:[Adhalin gene mutations in malignant limb-girdle muscular dystrophy and clinical features in adhalin-deficient muscular dystrophy]. 874 43

We report on a male patient aged 38, affected by a syndrome whose characteristic features include onset in early childhood, slow progression, diffuse muscle weakness, mental retardation and cardiomyopathy. Muscle biopsy showed myopathic changes compatible with muscular dystrophy. However, immunostaining for dystrophin as well as 50 and 43 kDa dystrophin-associated glycoproteins (DAGs) was normal. Genetic analysis suggested that direct involvement of the dystrophin gene was highly unlikely. No other family members were affected. Although the clinical picture is reminiscent of Duchenne/Becker muscular dystrophy, the immunologically and genetically documented lack of dystrophin involvement suggests that this particular syndrome is as yet undescribed.
 ...
PMID:Muscular dystrophy, mental retardation and cardiomyopathy not associated with dystrophin deficiency. 878 4

In order to characterize the nature of mutations occurring in non-deleted Duchenne (DMD) and Becker muscular dystrophy (BMD) affected males, a total of 40 unrelated Italian patients was studied for the presence of point mutations within the muscle-specific regulatory region of the dystrophin gene. We decided to investigate the dystrophin promoter sequences because nucleotide variations in these regions could impair the expression of the gene and be the underlying molecular defect in some forms of the disease. In four patients suffering from mental retardation, the brain promoter region was also studied. To screen for point mutations, we applied molecular analysis by parallel denaturing gradient gel electrophoresis (DGGE). No sequence alterations were found in either the muscle or the brain promoters, suggesting that mutations in these regions do not represent a common mechanism of mutation in DMD/BMD.
 ...
PMID:Mutational analysis of muscle and brain specific promoter regions of dystrophin gene in DMD/BMD Italian patients by denaturing gradient gel electrophoresis (DGGE). 880 15

We report the first C-terminal missense mutation in a Duchenne muscular dystrophy patient. A G10227A transition of the dystrophin gene was found which resulted in the substitution of a highly conserved cysteine at position 3340 within the second half of the dystroglycan-binding domain. Residual amounts of 427 kDa dystrophin were detected in western blot analysis of the patient's muscle tissue, and immunohistological examination revealed weak traces of dystrophin on all fibers. Sarcolemmal staining intensity of 43 kDa beta-dystroglycan was also reduced. Mental retardation in our patient and absence of the b-wave in his electroretinogram indicate that central nervous functions of dystrophin isoforms also depend on the presence of cysteine 3340.
 ...
PMID:A cysteine 3340 substitution in the dystroglycan-binding domain of dystrophin associated with Duchenne muscular dystrophy, mental retardation and absence of the ERG b-wave. 881 32

Duchenne muscular dystrophy (DMD) is a progressive degenerative lethal muscle disease. A significant proportion of DMD affected children suffer also from mental retardation. The rod shaped protein, dystrophin, which is absent from or defective in the muscle of DMD patients, binds to a number of membrane associated proteins (known collectively as dystrophin associated proteins [DAPs]). The levels of DAPs is greatly reduced in the muscle of DMD patients and mdx mice, which lack dystrophin. In addition to dystrophin isoforms, the DMD gene codes also for several smaller proteins. One of the small proteins, Dp71, is expressed in most or all non-muscle tissues and is the major DMD gene product in the brain. The function of the small DMD gene products is unknown. Here we show that mutant mice which do not express the smaller non-muscle products of the DMD gene have a reduced level of DAPs in their brain. This suggests that Dp71 is important for the formation and/or stabilization of a DAPs complex in brain.
 ...
PMID:Reduced levels of dystrophin associated proteins in the brains of mice deficient for Dp71. 887 69

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder primarily affecting young boys, often causing mental retardation in addition to the well-known progressive muscular weakness. Normal dystrophin expression is lacking in skeletal muscle and the central nervous system (CNS) of both DMD children and the mdx mouse model. The underlying biochemical lesion causing mental impairment in DMD is unknown. 1H-magnetic resonance spectroscopy (1H-MRS) detects choline-containing compounds, creatine and N-acetyl aspartate (NAA) in vivo. NAA is commonly used as a chemical marker for neurons, and a decline in NAA is thought to correlate with neuronal loss. Control mice were compared to mdx using a combination of in vivo and in vitro 1H-MRS methods to determine whether neural necrosis or developmental abnormalities occur in dystrophic brain. NAA levels were normal in mdx brain compared to controls suggesting minor, if any, neuronal necrosis in dystrophic brain. In contrast, choline compounds and myo-inositol levels were increased, indicative of gliosis or developmental abnormalities in dystrophic brain.
 ...
PMID:An in vivo and in vitro H-magnetic resonance spectroscopy study of mdx mouse brain: abnormal development or neural necrosis? 888 Jun 86

Major advances in the genetic understanding of the limb-girdle (LGMD) and congenital (CMD) muscular dystrophies have led to a new, genetically based classification of these disorders. The definition of the complex of dystrophin-associated proteins on a biochemical and subsequently genetic level has greatly accelerated this progress by providing candidate genes to complement or replace the process of linkage analysis either in families with muscular dystrophy or in sporadic cases. The major components of the dystrophin-associated proteins now known to be involved in muscular dystrophy besides dystrophin itself ar the sarcoglycan complex and the alpha 2-chain (merosin) of laminin-2 in the extracellular matrix. Mutations in the various sarcoglycans account for four types of autosomal recessive LGMD of varying severity (types 2C through 2F), including severe childhood-onset presentations. One type of autosomal recessive LGMD (type 2A) is caused by mutations in the protease calpain-3, whereas the gene for type 2B has not yet been identified, although the responsible locus has been assigned to chromosome 2p13. There are different autosomal dominant forms as well, one of which has been mapped to chromosome 5q31. With regard to CMDs, the major breakthrough involves a type of "classic" CMD with abnormalities of the white matter on magnetic resonance imaging of the brain. These patients show deficiencies of the laminin alpha 2-chain, and mutations in the corresponding gene have been identified. The group of laminin alpha 2-chain-positive classic CMD likely is heterogeneous. Among the group of CMDs with abnormalities of brain formation and mental retardation, genetic, immunohistochemical, and clinical differences are now beginning to emerge to help in the distinction between Fukuyama muscular dystrophy, the Walker-Warburg syndrome, and muscle-eye-brain disease.
 ...
PMID:Beyond dystrophin: current progress in the muscular dystrophies. 901 40

Dystrophin is present in various tissues other than skeletal and cardiac muscles, including the central nervous system (CNS) and the outer plexiform layer of the retina. Therefore lack of dystrophin might be related to mental retardation or to changes in electrophysiological tests exploring retina and CNS. We performed electroretinography, VEPs, BAEPs, SEPs and MEPs in 18 patients with Duchenne muscular dystrophy (DMD), 18 with Becker muscular dystrophy (BMD) and 12 obligate carriers. We observed a marked reduction of the b-wave amplitude in the scotopic ERG, mainly in DMD patients. Oscillatory potentials were altered in all groups, even in carriers, suggesting that dystrophin may be also involved in retinal circulation. VEPs changes confirmed the role of dystrophin in visual function. The other evoked potentials were altered only in a small percentage of subjects but changes of different tests did not overlap in individual subjects. Neurophysiological abnormalities did not correlate with type, site and size of alteration in the dystrophin gene.
 ...
PMID:Extra-muscle involvement in dystrophinopathies: an electroretinography and evoked potential study. 907 8


<< Previous 1 2 3 4 5 6 7 Next >>