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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report the sixth case of Menkes' kinky hair disease. This boy has been observed for as long as 16 months, and he his still alive at the time of publication. This genetic, X linked disorder of copper metabolism is always fatal in childhood. Diagnosis is evoked when is noted the conjunction of progressive cerebral degeneration, seizures, with pili torti and monilethrix. It can be asserted with the very low copper and cerulo-plasmin blood levels. Recognition of the disease in utero might be possible. New findings in skin' electron microscopy and hair' scanning electron microscopy are reported here. And two RX scanner of the brain have been performed.
Ann Dermatol Venereol 1978 May
PMID:[Menkes' disease (new skin and hair ultrastructural abnormalities) (author's transl)]. 70 42

Connective tissue disorders affecting skin can be inherited or acquired and might result from an alteration of structure, function or metabolism of the constitutive elements of the supporting matrix. Collagen, the protein building the fibrous framework of the dermis, is considered as an example in understanding such a pathology at the molecular level. The molecular structure, the polymerizing capacity and the degradation of this large protein depends upon the activity of several specific post-transcriptional enzymes operating inside or outside of the cells. Pathology is known to be associated with an altered activity of most of these enzymes. Several pathological skin conditions are defined at the level of their molecular defect as in several types of the Ehlers-Danlos syndrome, osteogenesis imperfecta. Menkes' kinky hair disease, epidermolysis bullosa and scurvy. A similar molecular pathogenesis can be logically hypothesized for various other processes involving connective tissue as in scleroderma, pretibial myxoedema, cheloids, Werner syndrome, aging and corticosteroid induced atrophy.
Ann Dermatol Venereol 1978 Nov
PMID:[Connective tissue diseases with cutaneous manifestation (author's transl)]. 75 6

The characteristic feature of Menkes' disease is a maldistribution of bodily copper; decreased copper levels are present in the serum, brain, and liver, whereas excess levels are present in gut, kidney, and most other nonhepatic tissues. Using cultured fibroblasts, we have shown that low extracellular copper concentrations induce synthesis of metallothionein, a copper-binding protein, in Menkes' cells but not in normal cells. This is due to a defect in a diffusable regulatory factor that is probably involved in copper metabolism. To further understand the role of the defective factor in transcription, assays have been developed to study the metal-dependent binding of nuclear proteins to metallothionein gene control sequences.
Arch Dermatol 1987 Oct
PMID:Metallothionein gene regulation in Menkes' syndrome. 366 72

Menkes' kinky-hair syndrome is an X-linked recessive neurodegenerative and connective-tissue disorder, with decreased serum copper and ceruloplasmin-copper oxidase concentrations and tissue-specific increases in copper content. Clinical manifestations can be related to relative copper deficiency and reduced activity of cuproenzymes in multiple organs. An animal model is provided by mice hemizygous for mutant alleles, such as the blotchy allele, at the X-linked mottled locus. This locus may be homologous in mouse and man. The basic defect is unknown but has been thought to reside in the regulation of the function or synthesis of metallothioneins. In the blotchy mouse and in cultured skin fibroblasts derived therefrom, we showed that the mutation specifically affects the metabolism of copper and not other trace metals. Excessive accumulation and abnormal (reduced) exit kinetics were demonstrated for copper but not for the related trace metals cadmium and zinc. While metallothionein-I messenger RNA (mRNA) concentrations were elevated in blotchy fibroblasts, the elevations in metallothionein-I mRNA in response to metallothionein inducers (cadmium, copper) were similar in blotchy and control cells. Further, metallothionein-I mRNA levels were indistinguishable in mutant and control fibroblasts containing equivalent intracellular copper concentrations. Finally, metallothionein-I mRNA content was not elevated in blotchy kidneys at early developmental stages, before storage of excessive copper. The aggregate data suggest that the basic defect in the blotchy mouse--and, by analogy, in Menkes' syndrome--does not reside in defective modulation of metallothionein function and does not cause abnormal regulation of metallothionein synthesis.
Arch Dermatol 1987 Nov
PMID:Regulation of copper metabolism in the mottled mouse. 367 14

Menkes's syndrome (trichopoliodystrophy) is an x-linked, recessive genodermatosis characterized by hair defects, severe retardation, convulsions, progressive neurologic deterioration, and early death. Recent studies in copper metabolism suggest that Menkes's syndrome may be a storage disease in which copper is irreversibly trapped in some tissues by metallothionein, a heavy-metal-binding protein. This then gives rise to a deficiency elsewhere, particularly in the brain, causing irreversible damage in the fetus. We present a patient with Menkes's syndrome and review the clinical and metabolic aspects of this disease.
Pediatr Dermatol 1984 Apr
PMID:Menkes's syndrome. 649 70

Menkes' syndrome is an X-linked recessive multisystem disease which is usually fatal prior to 5 years of age. Though originally felt to be a disorder of copper deficiency, it now appears to be a copper storage disease, with the observed defects resulting from inappropriate systemic copper distribution. Disorders in the metabolism of metallothionein, a metalloprotein involved in cellular copper transport, may be the primary defect in this syndrome. This review summarizes the relevant clinical and pathologic findings seen in this condition to date. It also describes some of the abnormalities in the metabolism of copper and metallothionein in these infants.
J Am Acad Dermatol 1983 Jul
PMID:Menkes' syndrome: an updated review. 688 97

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.
J Invest Dermatol 1994 Nov
PMID:Molecular pathology of the elastic fibers. 796 85

There has been considerable progress in chromosome mapping and gene identification in several severe hereditary skin diseases, leading to changes in genetic counseling. It is now possible to propose antenatal diagnosis to couples at risk based on an analysis of foetal DNA from trophoblast biopsies performed as early as the 9th week of gestation. Antenatal can be made by direct analysis based on identifying the mutation known in the family at risk or on indirect analysis based on the linkage disequilibrium of the allele or alleles associated with the disease in the family at risk. This method has already been shown to be effective in recessive dystrophic bullous epidermolysis, lethal Herlitz's junctional bullous epidermolysis, bullous ichthyosiform hereditary erythroderma, von Recklinghausen's neurofibromatosis, tyrosinase negative oculocutaneous albinism, Gorlin's syndrome, anhidrotic ectodermic dysplasia and Menkes disease. These techniques will replace microscopic examination of ultrastructure in foetal skin biopsies performed at 20 weeks gestation. They can also be applied to diseases where the antenatal diagnosis now relies on enzyme function tests or DNA distribution. Improving genetic counselling in these diseases requires the identification of the implicated genes, identification of the causal mutations in the families at risk and development of genetic markers for these diseases.
Ann Dermatol Venereol 1995
PMID:[Prenatal diagnosis of cutaneous genetic diseases by the study of fetal DNA]. 852 12

The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility. Considerable clinical and genetic heterogeneity exists, and more than nine separate forms have been recognized. Recent advances in the molecular analysis of EDS have identify defects responsible for EDS VI (homozygous and compound heterozygous mutations in the lysyl-hydroxylase gene), EDS VIIA and EDS VIIB (mutations in the type I collagene genes), EDS VIIC (deficiency of procollagen N-proteinase), EDS IX (mutations in the MNK gene), and EDS IV (mutations in the type III collagen gene). Of the various types of Ehlers-Danlos syndrome the most severe is type IV (EDS IV). Early studies showed that fibroblasts from EDS IV patients secreted lower than normal amounts of type III procollagen (Pope et al., 1975). Later, the disease was linked to COL3A1, the gene encoding this protein. More recently, with the publication of full length cDNA and partial characterisation of the gene structure, detailed analysis of mutations in EDS IV patients has become possible. Nineteen different mutations in the type III procollagen gene have been reported in different families with EDS IV. Recent results support the hypothesis that in EDS IV, dominant inheritance should be assumed, in sporadic cases also, unless proven otherwise. Very little is known about the genetics or biochemicals defects responsible for the others EDS subtypes, but with the applications of the tools of molecular biology, analysis of these defects if now within reach.
Ann Dermatol Venereol 1995
PMID:[Ehlers-Danlos syndromes. Clinical, genetic and molecular aspects]. 852 13

An alternative to using hair specimens for the study of inherited hair shaft defects has been to explore protein compositions in the context of hair formation. Hair follicles were obtained from patients with a hair disorder and the presumptive hair shaft (PHS) separated by microdissection for protein solubilization and electrophoretic experiments aimed at providing a new basis to help explain the mechanism of hair shaft defects. Two-dimensional electrophoresis (fluorographs) of labelled extracts was used to examine the major hair structural proteins and other polypeptide(s) found associated with PHS extracts in normal and aberrant specimens. Changes in either the intermediate filaments (IFs) or matrix polypeptides were not normally found in defective PHS specimens. The polypeptides showing greatest variation were associated with a PHS-specific component which was recently found in normal specimens. The variation in this polypeptide was manifested as multiple spots of different molecular weights. An investigation of the role of PHS-associated polypeptides as a likely part of the hair cross-linking mechanisms, involved examination of a PHS extract from a Menkes' patient. The observations suggest that formation of hair fibre shaft defects may be related to the status of PHS-associated polypeptides which could in turn be influenced by the presence of copper in the hair follicle.
Br J Dermatol 1996 Jul
PMID:Investigation of structural proteins in human hair defects using anagen follicles. 877 64


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