Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Keratins are heteropolymeric proteins which form the intermediate filament cytoskeleton in epithelial cells. Since 1991, mutations in several keratin genes have been found to cause a variety of human diseases affecting the epidermis and other epithelial structures. Epidermolysis bullosa simplex (EBS) was the first mechanobullous disease for which the underlying genetic lesion was found, with mutations in both the K5 and K14 genes rendering basal epidermal keratinocytes less resilient to trauma, resulting in skin fragility. The site of mutation in the keratin protein correlates with phenotypic severity in this disorder. Since mutations were identified in the basal cell keratins, the total number of keratin genes associated with diseases has risen to eleven. The rod domains of suprabasal keratins K1 and K10 are mutated in bullous congenital ichthyosiform erythroderma (BCIE; also called epidermolytic hyperkeratosis, EH) and mosaicism for K1/K10 mutations results in a nevoid distribution of EH. An unusual mutation in the VI domain of K1 has also been found to cause diffuse non-epidermolytic palmoplantar keratoderma (DNEPPK). Mutations in palmoplantar specific keratin K9 cause epidermolytic palmoplantar keratoderma (EPPK) and mutations in the late differentiation suprabasal keratin K2e cause ichthyosis bullosa of Siemens (IBS). In the last year or so, mutations were discovered in differentiation specific keratins K6a and K16 causing pachyonychia congenita type 1 and K17 mutations occur in pachyonychia congenita type 2. K16 and K17 mutations have also been reported to produce phenotypes with little or no nail changes: K16 mutations can present as focal non-epidermolytic palmoplantar keratoderma (NEPPK) and K17 mutations can result in a phenotype resembling steatocystoma multiplex. Recently, mutation of mucosal keratin pair K4 and K13 has been shown to underlie white sponge nevus (WSN). This year, the first mutations in a keratin-associated protein, plectin, were shown to cause a variant of epidermolysis bullosa associated with late-onset muscular dystrophy (MD-EBS). An unusual mutation has been identified in K5 which is responsible for EBS with mottled pigmentation and genetic linkage analysis suggests that the hair disorder monilethrix is likely to be due to a mutation in a hair keratin. The study of keratin diseases has led to a better understanding of the importance of the intermediate filament cytoskeleton and associated connector molecules in maintaining the structural integrity of the epidermis and other high stress epithelial tissues, as well as allowing diagnosis at the molecular level thus facilitating prenatal testing for this heterogeneous group of genodermatoses.
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PMID:Human keratin diseases: hereditary fragility of specific epithelial tissues. 902 91

The retroposon SINE-R.C2 was first identified as a human-specific insertion in the complement C2 gene. In our previous study, SINE-R type retroposons, derived from the endogenous retrovirus HERV-K family, have been found to be hominoid specific. In this report on human chromosome 13, we identified eighteen new SINE-R retroposons resembling those we have previously reported on the sex chromosomes and on chromosomes 7 and 17. Phylogenetic analysis using the neighbor-joining method revealed that four SINE-R retroposons (13-16, 21, 23, 25) on chromosome 13 were closely related to the human-specific retroposon SINE-R.C2, with a high degree of sequence homology (95-97%). Such elements differ from the HERV-K10. LTR sequence from which they are derived in being deleted for the promoter region. Therefore while the evidence adds to the case that some classes of SINE-R element have continued to proliferate in hominid and hominoid evolution and may, as in the case of Fukuyama type muscular dystrophy, be a cause of insertional mutagenesis, they are less likely than the HERV-K10 LTR to have a positive effect on host gene activity.
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PMID:Phylogenetic analysis of retroposon family as exemplified on human chromosome 13: further evidence for recent proliferation. 1090 Nov 76