Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menkes X-linked disease, a copper disturbance syndrome, is detectable in cell cultures. Prenatal findings in two at-risk foetuses suggested that prenatal diagnosis was also feasible. In this study, we report substantial evidence that therapeutic abortion can be limited to hemizygous males. Forty-two at-risk pregnancies from 21 European families and 1 Canadian family were monitored with 64Cu-uptake into cultured amniotic fluid cells. In 10 pregnancies with a male karyotype an affected foetus was predicted on the basis of the copper studies. The pregnancies were terminated and the diagnosis was in each case confirmed by a markedly increased placenta copper content. Fourteen male foetuses were predicted to be unaffected and none of them has developed signs of Menkes disease after birth. In 6 of these cases the diagnosis was checked in the newborn boy by placenta copper measurements, and they all had copper concentrations within normal limits. Eighteen pregnancies with a female karyotype were also studied, 9 females could be identified as carriers on the basis of the tissue culture studies or raised placenta copper values.
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PMID:Menkes X-linked disease: prenatal diagnosis of hemizygous males and heterozygous females. 734 14

A scanning proton microprobe has been used for the elemental microanalysis of individual fibroblast cells. Both normal fibroblasts and fibroblasts cultured from patients with Menkes' disease, an X-linked genetic disorder known to be associated with defective copper metabolism, were examined by the probe. The cells were cultured on a thin ultra-clean nylon foil and retained on that surface for analysis. The focused high-energy proton beam was used to irradiate selected individual cells and elemental information was derived from X-ray and backscattered proton data. The sensitivity of the scanning proton microprobe to trace concentrations of heavy elements has allowed this elemental information to be used to identify individual cells as being either normal or a Menkes' mutant. The cell identification was based on the application of discriminate analysis to a data set formed from the ratios of copper to each of the macroelements present in the cell. This method of cell identification offers the promise of rapid diagnosis of Menkes' disease.
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PMID:Elemental microanalysis of fibroblasts by a scanning proton microprobe and application to Menkes' disease. 751 17

Menkes' disease is a recessive X-linked disturbance of copper metabolism, resulting in accumulation of copper in several extra-hepatic tissues including the placenta. Metallothionein (MT) is a low-molecular weight protein with a high affinity for group II metal ions, such as copper. Its synthesis is induced by the presence of the ions. The aim of this study was to investigate the pattern of the MT immunoreactivity in placental tissue obtained from women at-risk of Menkes' disease in order to examine whether the MT occurrence and distribution may reflect the copper content. Placental tissue from six women with a family history of Menkes' disease, from 4 women without a family history, and from 2 hydatiform moles was studied. Positive MT immunostaining was found to be independent of the length of fixation, whether the tissue samples were fixed in 4% buffered formaldehyde or Bouin's fixative. The avidin-biotin-complex (ABC)-technique was used. The copper content was measured by neutron activation analysis (NAA). In all placental tissue sections positive MT immunostaining appeared only in the trophoblast and only in proliferating cells. In placental tissue sections obtained from foetuses and children affected by Menkes' disease an additional MT immunostaining appeared in the Hofbauer cells of the chorionic villi. This staining was associated with an increased content of copper as measured by NAA. We conclude that the immunohistochemical demonstration of MT reflects the copper content and may be useful in pre- and postnatal diagnosis of Menkes' disease.
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PMID:Metallothionein expression in placental tissue in Menkes' disease. An immunohistochemical study. 757 74

Two highly polymorphic CA repeats have been identified in the Menkes gene (ATP7A). These repeats should be useful for prenatal diagnosis and carrier detection in families with Menkes disease and X-linked cutis laxa. The observed heterozygosity for these two repeats was 0.778 and 0.60 in Centre d'Etude du Polymorphisme Humaine (CEPH) families.
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PMID:Two highly polymorphic CA repeats in the Menkes gene (ATP7A). 764 57

Menkes' disease, a neurodegenerative progressive X-linked disorder, was diagnosed in a 4-month-old child. The diagnosis was made on the combination of clinical features with laboratory and radiological findings. The pathogenesis of the skeletal findings in Menkes' disease is as yet unclear. Because of the severity of the prognosis and in order to plan treatment, the correct diagnosis has to be reached quickly. Typical manifestations of the syndrome are likely to develop after 3 months of age, with a pleiotropic appearance. In the present case, on the basis of the clinical investigation the patient underwent retrograde cystourethrography, roentgenographic examination of the skeleton, and magnetic resonance imaging of the brain. On analysis of the magnetic resonance imaging, we detected one-sided involvement of both subcortical and cortical parenchyma resembling a unilateral ischemic lesion such as, to our knowledge, has not yet been reported.
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PMID:Radiological findings in a case of Menkes' disease. 775 9

Wilson disease is an autosomal recessive disorder of copper transport. Disease symptoms develop from the toxic build-up of copper primarily in the liver, and subsequently in the brain, kidney, cornea and other tissues. A candidate gene for WD (ATP7B) has recently been identified based upon apparent disease-specific mutations and a striking amino acid homology to the gene (ATP7A) responsible for another human copper transport disorder, X-linked Menkes disease (MNK). The cloning of WD and MNK genes provides the first opportunity to study copper homeostasis in humans. A preliminary analysis of the WD gene is presented which includes: isolation and characterization of the 5'-end of the gene; construction of a genomic restriction map; identification of all 21 exon/intron boundaries; characterization of extensive alternative splicing in brain; prediction of structure/function features of the WD and MNK proteins which are unique to the subset of heavy metal-transporting P-type ATPases; and comparative analysis of the six metal-binding domains. The analysis indicates that WD and MNK proteins belong to a subset of transporting ATPases with several unique features presumably reflecting their specific regulation and function. It appears that the mechanism of alternative splicing serves to regulate the amount of functional WD protein produced in brain, kidney, placenta, and possibly in liver.
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PMID:Characterization of the Wilson disease gene encoding a P-type copper transporting ATPase: genomic organization, alternative splicing, and structure/function predictions. 783 24

The connective-tissue disorder occipital horn syndrome (OHS) is hypothesized to be allelic to Menkes disease. The two diseases have different clinical presentations but have a similar abnormality of copper transport. Mice hemizygous for the blotchy allele of the X-linked mottled locus have similar connective-tissue defects as OHS and may represent a mouse model of this disease. We have analyzed the Menkes/mottled copper-transporting ATPase in these two potentially homologous disorders and have identified similar splicing mutations in both. Some expression of normal mRNA was detectable by reverse transcription-PCR in the mutant tissues. These findings contrast with the more debilitating mutations observed in Menkes disease and suggest that low amounts of an otherwise normal protein product could result in the relatively mild phenotype of OHS and of the blotchy mouse.
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PMID:Similar splicing mutations of the Menkes/mottled copper-transporting ATPase gene in occipital horn syndrome and the blotchy mouse. 788 10

Elastic fibers form a network that contributes to the elasticity and resilience of tissues such as the skin. Histopathologic and ultrastructural abnormalities in the elastic fibers have been observed in several diseases of the skin and other tissues. Recent cloning of several genes involved in elastic fiber architecture has lead to the approach of the study of elastic fiber genodermatoses through molecular analysis. However, in genodermatoses, such as pseudoxanthoma elasticum, many of the genes encoding elastic fiber components have been excluded by genetic linkage analysis. In recent years, mutations in several of the genes encoding elastic fiber proteins have been demonstrated in other diseases. These include mutations in the fibrillin 1 gene in the Marfan syndrome, and genetic linkage of congenital contractural arachnodactyly to fibrillin 2, and, most recently, demonstration of abnormalities in the Menkes syndrome gene in X-linked cutis laxa. The first disorders to involve mutations in the elastin gene itself are, surprisingly, cardiovascular and neurobehavioral disorders, such as supravalvular aortic stenosis and Williams syndrome. These findings suggest that additional, as yet undiscovered, components of the elastic fiber network in the skin may hold the key to unraveling the molecular basis of the elastin-related genodermatoses.
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PMID:Molecular pathology of the elastic fibers. 796 85

The mottled mouse has been proposed as an animal model for Menkes disease, an X-linked disorder of copper transport. The recent isolation of a copper-transporting ATPase gene responsible for Menkes disease has allowed us to test this hypothesis. Here we report the isolation and sequence of the mouse homologue of this gene. We show that two mottled (Mo) alleles, dappled (Modp) and blotchy (Moblo), have abnormalities in the murine mRNA and that Modp has a partial gene deletion. These studies prove that the mottled mouse is the murine model for Menkes disease, providing the basis for future biochemical and therapeutic studies.
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PMID:The mottled gene is the mouse homologue of the Menkes disease gene. 772 11

A rare case of a long-term survivor of Menkes' syndrome who was treated early and had excision of bilateral axillary skin excess is presented. Primary wound healing was observed and skin histology showed fragmentation of the elastic fibers. Two years after surgery, the scars appeared atrophic with evidence of early recurrence of the skin excess. The relationship between Menkes' syndrome and the other copper-related syndromes (X-linked cutis laxa, occipital horn syndrome, and Ehlers-Danlos syndrome type 1X) is also described.
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PMID:Menkes' syndrome: wound healing in a long-term survivor. 806 85


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