Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O75695 (X-linked recessive)
 2,041 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The muscle provocation test (MPT: 40 min of strenuous exercise on a bicycle ergometer) is a sensitive method for the detection of carriers of Duchenne muscular dystrophy. The diagnostic applicability of MPT for carrier detection in X-linked Becker muscular dystrophy is demonstrated. Obligate carriers with mean creatine kinase (CK) values on repeated determination within the normal range showed a greater CK elevation after MGP than control subjects. Three of seven daughters of obligate carriers with normal resting CK activity had increased CK activity after MPT. These data suggest that the use of MPT may enhance the capability to discriminate carriers for these X-linked recessive genes.
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PMID:Carrier detection in X-linked Becker muscular dystrophy by muscle provocation test (MPT). 666 70

Two healthy men with McLeod syndrome, a rare X-linked recessive phenotype characterized by acanthocytosis and weakened red blood cell antigenicity in the Kell blood group system, have been investigated. Both men showed raised blood creatine kinase levels, with myopathic EMG abnormalities. Biopsies of the quadriceps muscle showed the features of an active myopathy although there was no clinical evidence of muscular abnormality. The combination of the association of membrane abnormalities in red blood cells and a myopathy in both McLeod phenotype and Duchenne muscular dystrophy suggests that these syndromes may be due to related genetic abnormalities. The genetic locus for McLeod phenotype is situated near the end of the short arm of the X chromosome. The locus for Duchenne muscular dystrophy is unknown but it has been postulated that it is also situated on the short arm of the X chromosome at Xp 21. The occurrence of a subclinical X-linked myopathy with acanthocytosis (McLeod phenotype) thus raises the possibility of a new approach to genetic investigations in Duchenne muscular dystrophy, and in the related milder forms of this disease.
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PMID:Benign X-linked myopathy with acanthocytes (McLeod syndrome). Its relationship to X-linked muscular dystrophy. 668 53

Benefit-to-cost analysis (using standard economic methods) and the predictive tools of genetics are important in the assessment of genetic services for high burden, single gene disorders. We have studied 6 generations of a 167-member, stable, North Georgia kindred at risk for X-linked recessive humeroperoneal neuromuscular disease with cardiac conduction defects. This disorder began in affected males in the teen years, with total disability expected by the 3rd decade and death by age 50. Using known fecundity rates and Mendelian probabilities, 26.6 heterozygous females and 9.4 hemizygous affected males were expected in the currently developing generation. We compared the compensatory costs for families with affected males against costs of genetic intervention for this disorder. All costs and benefits were discounted to present values at 6% and 10% and a benefit-to-cost ratio was derived. At a 6% discount rate the benefit-to-cost ratio was 21 to 1 while at a 10% discount rate the benefit-to-cost ratio was 14 to 1. We conclude that although this is an unusual X-linked muscular dystrophy, it constitutes a prototypic public and private expense which is largely preventable. The method of cost accounting within pedigrees has wide applicability. The results reemphasize the economic benefit of comprehensive public health programs in genetics, particularly in areas with stable, high risk-populations.
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PMID:Application of benefit-to-cost analysis to an X-linked recessive cardiac and humeroperoneal neuromuscular disease. 678 79

We studied a family in which three boys had both Duchenne muscular dystrophy and hemophilia A. Seven other males had only hemophilia A. Genetic linkage study showed a maximum likelihood estimate of recombination frequency of these two X-linked recessive traits of 0.16 with 95% confidence limits of 0.045 and 0.50. The loci of the two diseases may be closer than previous estimates.
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PMID:Genetic linkage study of Duchenne muscular dystrophy and hemophilia A. 720 58

Haldane's rule states that one-third of the cases of an X-linked recessive lethal should represent new mutations. This rule is derived under the assumptions that there is equilibrium between mutation and selection, that mutation rates in ova and sperm are equal, and that heterozygous and homozygous normal women have the same fitness. To test this rule for Duchenne muscular dystrophy (DMD), we have examined the mothers of 55 boys with DMD (16 familial and 39 isolated cases) and classified them as carriers or noncarriers on the basis of measures of ribosomal protein synthesis (RPS). Of the 55 mothers, only nine (16.4%) are classified as noncarriers, a figure significantly different from the expected one-third. When the analysis is limited to the 39 mothers of isolated cases, 23.1% (9/39) are classified as noncarriers, still significantly different than expected under Haldane's rule. Violation of any of the assumptions under which Haldane's rule is derived could lead to deviations from the expected one-third new mutants. We find the most likely explantation to be a higher male than female mutation rate. This is supported also by the finding that maternal grandfathers in whom a mutation occurred had higher mean age at birth of the carrier daughter (33.7 +/- 1.6) than did the general population or intrapedigree controls (29.5 +/- 1.3).
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PMID:Frequency of new mutants among boys with Duchenne muscular dystrophy. 721 51

The severe Duchenne type of muscular dystrophy is inherited as an X-linked recessive trait. Approximately two thirds of healthy female heterozygous carriers have a high serum creatine kinase (SCK). A suspected carrier with a normal SCK level therefore, presents an important problem in genetic counselling. Based on Bayesian methods, Emery and Hollyway derived a formula which is applicable when the sporadic case is either the son or brother of a consultant and which also includes information on SCK levels in the consultant and in normal daughters and sisters. The present paper describes the results obtained with use of this formula in 27 families with at least a propositus with Duchenne muscular dystrophy.
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PMID:[Estimation of the probability of heterozygosity in Duchenne-type progressive muscular dystrophy]. 728 70

Determination of serum creatine phosphokinase (CPK) activity is often used in efforts to detect carriers of X-linked muscular dystrophies. We have recently demonstrated that another serum enzyme, pyruvate-kinase (PK) may also be of use in the diagnosis of patients affected with a variety of neuromuscular disorders. To evaluate the usefulness of this assay for carrier detection, a comparative study of serum PK and CPK activity was performed in 74 female relatives of patients affected with Duchenne (DMD) and Becker (BMD) muscular dystrophies. For obligate carriers of the DMD gene, 10 of 14 had elevated CPK's, 11 of 14 had elevated PK's and 12 of 14 had abnormal results for either of the two enzymes. Three of 16 mothers of isolated cases had increased serum CPK activity and 6 of 16 had increased PK activity (7 had elevation of at least one enzyme). These preliminary data suggest that the use of PK may enhance the capability to discriminate carriers for these X-linked recessive genes.
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PMID:Serum pyruvate-kinase (PK) and creatine-phosphokinase (CPK) in female relatives and patients with X-linked muscular dystrophies (Duchenne and Becker). 738 16

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder with a high spontaneous mutation rate and no effective treatment, hence development of genetic based therapies is an important goal. We report that expression of a recombinant human minidystrophin cDNA, compatible with current viral vectors, can significantly reduce the myopathic phenotype in transgenic mdx mice, even when expressed at only 20-30% of endogenous dystrophin levels at the sarcolemma. To the extent that data obtained in mouse studies are applicable to DMD, the virtual elimination of morphological and biochemical abnormalities in the mdx mouse supports the use of this cDNA in somatic gene therapy protocols for DMD.
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PMID:Expression of human full-length and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophy. 758 60

A twin pregnancy following in vitro fertilization-embryo transfer coincidentally at risk for the X-linked recessive Duchenne muscular dystrophy is described. First-trimester prenatal diagnosis by transabdominal chorionic villus samplings on the dichorionic placentae and molecular linkage analysis could exclude the disorder in both fetuses. Genetic counseling and prenatal diagnosis were particularly complex due to the twin pregnancy, the need for linkage analysis, and confined placental mosaicism 45,X/46XX in one of the fetuses. All parties should be aware that additional invasive diagnostic procedures in the second trimester might be required. It is proposed that, in similar situations, only one, arguably two, fertilized egg be transferred at a time to facilitate prenatal diagnosis and decision making for these rare couples. This problem, however, may be increasingly overcome by preimplantation diagnosis.
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PMID:Complex genetic counseling and exclusion of Duchenne muscular dystrophy in a twin pregnancy after in vitro fertilization (IVF). 782 43

Duchenne (DMD) and Becker (BMD) muscular dystrophy are allelic X-linked recessive diseases caused by a mutation in the dystrophin gene located on the short arm of chromosome X (Xp21). The dystrophin gene is the largest gene known in humans, extending over 2300 kb and containing more than 70 exons coding for a 420 KD protein comprising 3685 amino acids. The gene is highly unstable, with a high percentage of deletions and rearrangements. A third of dystrophin mutations are new mutations. The frequency of DMD is 1:3500 liveborn males, and that of BMD 1:10000. These dystrophies are severe, progressive, and lethal. BMD/DMD patients and 2/3 of female carriers have high levels of creatine phosphokinase (CK). During the past 5 years, 169 families with patients affected by progressive muscular dystrophy were examined and counselled. We were able to exclude the diagnosis of DMD/BMD in 49 families on the basis of clinical symptoms and signs, normal dystrophin on biopsy (11 families) and/or the absence of linkage to chromosome X by analysis of RFLP derived haplotypes. Molecular analysis was performed on 111 DMD/BMD families (five BMD and 106 DMD) with 81 available probands. This study resulted in the establishment in Israel of an integrated diagnostic protocol for DMD/BMD, employing genetic, biochemical and molecular techniques. Molecular analysis provided most of the families with new and essential information.
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PMID:A molecular survey of Israeli Duchenne and Becker muscular dystrophy patients. 785 72


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