Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A systematic review of the more than 2,000 genetic loci of man cataloged by McKusick indicated that approximately 7% may play a role in modulating the rates of development of various aspects of the senescent phenotype. Assuming an upper limit of about 100,000 loci in man, numerous alleles at approximately 7,000 loci could be contributing to characteristic patterns of aging in individual human beings. Point mutations or chromosomal aberrations involving such loci may result in various progeroid syndromes. These have been classified into two categories: segmental progeroid syndromes, which involve multiple aspects of the senescent phenotype, and unimodal progeroid syndromes, in which predominantly one aspect of the phenotype is involved. Two different examples of segmental progeroid syndromes were discussed: the Werner syndrome (an autosomal recessive) and the Down syndrome (trisomy 21). Examples of unimodal progeroid syndromes included familial hypercholesterolemia (accelerated atherogenesis), xeroderma pigmentosum (acceleration of skin aging, including age-related neoplasms), and certain forms of intestinal polyposis (acceleration of adenocarcinoma of the colon). It is remarkable and encouraging that the biochemical genetic basis of many progeroid syndromes, including all of those mentioned above, may be amenable to investigation with cultured mesenchymal somatic cells from individual subjects. For example, cells from patients with the Werner's syndrome have a striking limitation of their in vitro replicative life-spans and undergo extensive chromosomal rearrangements. These abnormalities are presumably related to an enzyme deficiency which, in principle, could be identified by biochemical studies of cultured cells.
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PMID:Syndromes of accelerated aging. 621 19

The easy accessibility of the skin as a therapeutic target provides an exciting potential for this organ for the development of gene therapy protocols for cutaneous diseases and a variety of metabolic disorders. Thus far, full phenotypic reversion of a diseased phenotype has been achieved in vivo for junctional epidermolysis bullosa and X-linked or lamellar ichthyosis and in vitro for xeroderma pigmentosum. These recessive skin diseases are characterized by skin blistering, abnormalities in epidermal differentiation and increased development of skin cancers, respectively. Corrective gene delivery at both molecular and functional levels was achieved by transduction of cultured skin cells using retroviral vectors carrying the specific curative cDNA. These positive results should prompt clinical trials based on transplantation of artificial epithelia reconstructed ex vivo using genetically modified keratinocytes. Promising results have also been obtained in phenotypic reversion of cells isolated from patients suffering from a number of metabolic diseases such as gyrate atrophy, familial hypercholesterolemia or phenylketonuria. In these diseases transplantation of autologous artificial epithelia expressing the transgenes of interest or direct transfer of the DNA to the skin represents a potential therapeutic approach for the systemic delivery of active molecules. Successful cutaneous gene therapy trials, however, require development of protocols for efficient gene transfer to epidermal stem cells, and information about the host immune response to the recombinant polypeptides produced by the implanted keratinocytes. The availability of spontaneous animal models for genodermatoses will validate the gene therapy approach in preclinical trials.
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PMID:Cutaneous gene transfer and therapy: the present and the future. 1126 32