Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Assay of serum creatine kinase activity is useful in the detection of carriers of the X-linked gene for Duchenne muscular dystrophy (DMD). For genetic counselling this assay has been used in conjunction with pedigree analysis to improve estimates of the risk that a female relative of a DMD patient is a carrier. To measure the impact of the program, follow-up information was obtained from women who had received genetic counselling for DMD. Their responses showed that the risk of producing an affected son had been a major factor in their attitude toward family planning, and their reproductive performance correlated inversely with their genetic risk. The decision by the majority of proven carriers to prevent the birth of further male offspring was reflected in a recent decline in the frequency of a known family history of DMD among newly ascertained cases.
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PMID:Carrier detection and genetic counselling in Duchenne muscular dystrophy: a follow-up study. 97 64

Duchenne and Becker muscular dystrophies (DMD and BMD) are two allelic recessive X-linked disorders. Molecular deletions of various regions of the dystrophin gene are the main mutations detected in DMD and BMD patients. Molecular study of DMD and BMD DNA are instrumental to understand the pathological molecular mechanisms and the function of the protein. We describe here dystrophin and its interaction with a glycoprotein complex and we then focus on two particular patients with partial deletions of the dystrophin gene: 1) a typical Becker patient, who shows an intragenic deletion disrupting the reading frame. We describe in this case alternative splicings restoring the reading frame, which might explain the mild clinical phenotype of this patient, 2) a deletion of the distal part of the DMD gene coding for the carboxyterminal domain of the dystrophin in a young patient. The normal localization of dystrophin at the inner face of the plasma membrane in the muscle of this patient suggests that the last domain of this protein is not sufficient to anchor dystrophin at the membrane.
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PMID:[Molecular pathology of Duchenne and Becker muscular dystrophy]. 130 Dec 22

Cognitive impairment occurs in one-third of patients with Duchenne muscular dystrophy, a lethal X-linked, recessive disease caused by mutations in the dystrophin gene which is expressed in both brain and muscle, the two transcripts having alternative first exons. Previous reports have indicated that the 'brain-type' dystrophin transcript predominates in brain. Using in situ hybridisation with antisense oligonucleotides, expression of four distinct mRNAs in specific brain areas is demonstrated here; the 14 kb muscle-type and brain-type transcripts were found to coexist in cortical and hippocampal neurons and two new transcripts have been identified in dentate gyrus and cerebellar Purkinje neurons, respectively. The latter has a novel first exon which was isolated and sequenced from mouse and human, and which would encode a protein with a different amino-terminus from the known muscle- and brain-type isoforms. Mapping in human located this exon in a large intron between the muscle-type promoter and second exon of the dystrophin gene. This finding of four alternative transcripts regulated by different promoters in brain reveals a new complexity to dystrophin expression that may have important insights for mental retardation mechanisms.
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PMID:Expression of four alternative dystrophin transcripts in brain regions regulated by different promoters. 130 51

X-linked congenital stationary night blindness (XL-CSNB) is a nonprogressive disorder of the retina, characterized by night blindness, reduced visual acuity, and myopia. Previous studies have localized the CSNB1 locus to the region between OTC and TIMP on the short arm of the X chromosome. We have carried out linkage studies in three XL-CSNB families that could not be classified as either complete or incomplete CSNB on the criteria suggested by Miyake et al. (1986. Arch. Ophthalmol. 104: 1013-1020). We used markers for the DXS538, DMD, OTC, MAOA, DXS426, and TIMP loci. Two-point analyses show that there is close linkage between CSNB and MAOA (theta max = 0.05, Zmax = 3.39), DXS426 (theta max = 0.06, Zmax = 2.42), and TIMP (theta max = 0.07, Zmax = 2.04). Two multiply informative crossovers are consistent with CSNB lying proximal to MAOA and distal to DXS426, respectively. Multipoint analysis supports this localization, giving the most likely order as DMD-17 cM-MAOA-7.5 cM-CSNB-7.5 cM-DXS426/TIMP-cen, and thus refines the localization of CSNB.
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PMID:Linkage analysis in X-linked congenital stationary night blindness. 142 34

Duchenne muscular dystrophy (DMD) is a common, lethal, chromosome X-linked inherited disease. Moderate cognitive impairment is a feature of DMD, but the underlying mechanisms are unknown. DMD is characterized by a defect in a protein, dystrophin, that is located predominantly in muscle but has been detected in brain. We sought to directly localize dystrophin within the complex synaptic structure of the cerebral cortex by focusing on the postsynaptic density (PSD), which appears to be central to synaptic function. We report that a specific anti-dystrophin antibody (anti 6-10) recognizes three distinct proteins in the purified PSD: the 400-kDa dystrophin and two previously unidentified dystrophin-related proteins of 120 and 110 kDa. These proteins exhibited differential regional expression in PSDs from cerebral cortex, cerebellum, and olfactory bulb. In the cortical PSD, the 400-kDa dystrophin was predominant, whereas the 120-kDa protein was the major species in cerebellum and olfactory bulb PSDs. The three proteins were differentially expressed in the PSD during cortical development: the 400-kDa protein exhibited a selective 9-fold increase during postnatal days 7 to 10, suggesting a normal physiological role in synaptic maturation. The PSD from the mdx mouse, a model of human DMD, contained no detectable 400-kDa dystrophin but expressed the two dystrophin-related proteins. Our results indicate that brain dystrophins are localized to the PSD, potentially as three isoforms, and raise the possibility that cognitive abnormalities in DMD are attributable to synaptic dysfunction associated with deficits in brain dystrophin molecules.
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PMID:Detection of dystrophin in the postsynaptic density of rat brain and deficiency in a mouse model of Duchenne muscular dystrophy. 145 57

The percentage of subjects with contractures, mean maximal loss of range, and relative contracture indices are reported in 230 patients, with 11 diseases seen in a neuromuscular disease clinic during a five-year period. The highest percentage of contractures occurred in patients with Duchenne muscular dystrophy. The number of contractures was significantly greater (p less than .001) (1) in the lower than in the upper extremities; (2) in diseases considered myopathic than in those considered neuropathic; (3) in diseases that are X-linked than in those that are not; and (4) in rapidly progressive than in slowly progressive diseases.
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PMID:Contractures in neuromuscular disease. 151 88

The X-linked gene responsible for Duchenne muscular dystrophy encodes dystrophin, a high-molecular-weight cytoskeletal protein. Studies in several laboratories have revealed deletion of one or more exons in 60% of affected boys; quantitative analysis in our laboratory has detected duplication of exons in another 6%. The severe Duchenne phenotype is associated with deletions or duplications that shift the reading frame of the message, whereas the milder Becker muscular dystrophy is associated with deletions or duplications that maintain the reading frame. Patients who have neither deletion nor duplication may have nonsense mutations, one of which has been detected by predicting the site of the mutation from the size of the truncated protein. Rare females with the disease have a translocation that disrupts the dystrophin gene on one X chromosome and causes non-random inactivation of the normal X, resulting in the expression of the disease. The high frequency of new mutation provides an opportunity to study the mechanism of chromosomal rearrangement that is characteristic of the disease. Our laboratory has focused on the translocations in females and on duplications in affected males. The X-autosome translocations of affected females are all de novo events that originated in the paternal set of chromosomes. Molecular characterization of the translocation junctions revealed reciprocal translocation with both deletion and addition of nucleotides at the junction, suggestive of a breakage and reunion mechanism. Duplications studied to date are all tandem in nature and sequence analysis of duplication junctions has revealed both homologous and non-homologous recombination. Marker segregation analysis has revealed that five out of five duplications originated in a single X chromosome of one of the maternal grandparents, suggesting that the recombination event is unequal sister chromatid exchange.
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PMID:Duchenne muscular dystrophy: gene and gene product; mechanism of mutation in the gene. 152 15

Duchenne muscular dystrophy (DMD) results from mutations in the X-linked gene coding for the muscular protein dystrophin. The isolation of genomic and cDNA probes for this gene has greatly facilitated the detection of DMD carriers, which previously relied mainly on measurements of serum creatine kinase (CK), and has enabled prenatal diagnosis of this disease. However, the relatively large size of the gene and the high frequency of recombination and mutation events within the dystrophin locus continue to pose difficulties in the genetic counselling and prenatal diagnosis of DMD, and render the conclusions of molecular analysis less clear cut. This communication presents examples of two such difficulties: the distinction between sporadic and inherited cases in families with a single patient and normal CK levels in all females, and the distinction between mutant and normal dystrophin alleles in families in which the patients have died. The combined use of genomic and cDNA probes allows one to make these distinctions. An additional complicating factor, gonadal mosaicism, is demonstrated.
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PMID:Use of dystrophin genomic and cDNA probes for solving difficulties in carrier detection and prenatal diagnosis of Duchenne muscular dystrophy. 153 62

Golden retriever muscular dystrophy (GRMD) is a spontaneous, X-linked, progressively fatal disease of dogs and is also a homologue of Duchenne muscular dystrophy (DMD). Two-thirds of DMD patients carry detectable deletions in their dystrophin gene. The defect underlying the remaining one-third of DMD patients is undetermined. Analysis of the canine dystrophin gene in normal and GRMD dogs has failed to demonstrate any detectable loss of exons. Here, we have demonstrated a RNA processing error in GRMD that results from a single base change in the 3' consensus splice site of intron 6. The seventh exon is then skipped, which predicts a termination of the dystrophin reading frame within its N-terminal domain in exon 8. This is the first example of dystrophin deficiency caused by a splice-site mutation.
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PMID:An error in dystrophin mRNA processing in golden retriever muscular dystrophy, an animal homologue of Duchenne muscular dystrophy. 157 76

X-linked dystrophinopathy is the most common cause of isolated cases of myopathy in males. To investigate dystrophin abnormalities as a cause of myopathy in girls and women, we used dystrophin immunocytochemistry to study muscle biopsies from 505 girls and women with neuromuscular disease. Forty-six muscle biopsies showed a combination of fibers containing or lacking dystrophin; this mosaic immunostaining pattern denoted a carrier status. Twenty-one of 46 (45.6%) had a family history of Duchenne muscular dystrophy in males. Twenty-five of 46 (54.3%) were isolated cases, with no previous family history of neuromuscular disorder. The laboratory findings of the isolated cases were consistent with the familial cases; all showed myopathic histopathology and abnormal elevations of serum CK. The clinical presentations of the isolated cases varied but were consistent with the familial cases: 40% (10/25) of isolated cases showed proximal limb weakness before age 10, 24% (6/25) presented with myalgias or cramps, 24% (6/25) presented with incidental findings of grossly elevated CK levels, 8% (2/25) noted easy fatigue, and 4% (1/25) had slowly progressive proximal limb weakness beginning at age 45. From our data, the clinical criteria for consideration of an underlying dystrophinopathy in isolated female cases of myopathy are CK levels greater than 1,000 IU/l and myopathic histopathology. About 10% of the isolated cases of hyperCKemic myopathy (25/210) were proven by dystrophin analysis to have a dystrophinopathy as the cause of their disease (manifesting carriers of Duchenne dystrophy). However, we feel that this may be an underestimate. The correct diagnosis in these patients is imperative for appropriate genetic counseling to the patients and their families.
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PMID:Dystrophinopathy in isolated cases of myopathy in females. 157 51


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