Disease relevance of KRT10

• Splice site and deletion mutations in keratin (KRT1 and KRT10) genes: unusual phenotypic alterations in Scandinavian patients with epidermolytic hyperkeratosis [1].
• OBJECTIVES: To describe an autosomal recessive, mild, nonpalmar/plantar epidermolytic ichthyosis segregating in an extended pedigree of Norfolk terrier dogs due to a splice-site mutation in the gene encoding keratin 10 (KRT10) [2].
• R162W was detected in five unrelated families and affects the corresponding residue in the keratin 14 and keratin 10 genes that is also altered in cases of epidermolysis bullosa simplex and generalised epidermolytic hyperkeratosis, respectively [3].
• Delays in malignant tumor development in transgenic mice by forced epidermal keratin 10 expression in mouse skin carcinomas [4].
• And palmoplantar keratoderma (PPKD) can be an accompanied symptom caused by either K1 or K10 mutation [5].

Psychiatry related information on KRT10

• METHODS: Three SMI screening scales were developed for possible use in the SAMHSA National Household Survey on Drug Abuse: the Composite International Diagnostic Interview Short-Form (CIDI-SF) scale, the K10/K6 nonspecific distress scales, and the World Health Organization Disability Assessment Schedule (WHO-DAS) [6].
• The performance of the K6 and K10 screening scales for psychological distress in the Australian National Survey of Mental Health and Well-Being [7].
• CONCLUSIONS: While the K10 might outperform the K6 in screening for severe disorders, the K6 is preferred in screening for any DSM-IV mood or anxiety disorder because of its brevity and consistency across subsamples [7].
• RESULTS: Both the K10 and K6 have good precision in the 90th-99th percentile range of the population distribution (standard errors of standardized scores in the range 0.20-0.25) as well as consistent psychometric properties across major sociodemographic subsamples [8].

High impact information on KRT10

• We studied the K1 and K10 genes in blood and in the keratinocytes and fibroblasts of lesional and nonlesional skin from three patients with epidermal nevi and four of their offspring with epidermolytic hyperkeratosis [9].
• In the patients with epidermal nevi, point mutations in 50 percent of the K10 alleles of epidermal cells were found in keratinocytes from lesional skin; no mutations were detected in normal skin [9].
• In the offspring with epidermolytic hyperkeratosis, the same mutations as those in the parents were found in 50 percent of the K10 alleles from all cell types examined [9].
• The correlation of mutations in the K10 gene with lesional skin and the correlation of the normal gene with normal skin provide evidence that genetic mosaicism can cause clinical mosaicism [9].
• We show that KPPF co-segregates with a rare, high molecular weight allele of an insertion-deletion polymorphism in the C-terminal coding region of the keratin 10 gene (Z = 8.36 at theta = 0.00) and segrates as a true autosomal dominant trait [10].

Chemical compound and disease context of KRT10

• Arginine in the beginning of the 1A rod domain of the keratin 10 gene is the hot spot for the mutation in epidermolytic hyperkeratosis [11].
• An alanine to proline mutation in the 1A rod domain of the keratin 10 chain in epidermolytic hyperkeratosis [12].
• In addition to the expression of suprabasal markers such as cytokeratin 10 and involucrin, carcinomas also express cytokeratin 8 and 18 [13].
• Using image analysis, these markers were measured in the epidermis in a standardized manner.Treatment of psoriasis with short-term topical steroid resulted towards normalization of Ki-67 antigen, beta-1 integrin, keratin 10 and keratin 6 expression, which are parameters for proliferation and differentiation [14].
• The most frequent mutation that causes the autosomal dominant skin disease epidermolytic hyperkeratosis (EHK) is an arginine to histidine substitution at position 10 in the 1A segment of the rod domain of keratin 10 [15].

Biological context of KRT10

• In this study, we tested the hypothesis that the EHK phenotype is linked to one of the suprabasilar keratins (KRT10 or KRT1) present in the types I and II keratin gene clusters in chromosomes 17q and 12q, respectively [16].
• Codon deletions were found in KRT1 (delta170-173) and in KRT10 (delta161-162) in two patients with a severe phenotype [1].
• Two of the point mutations were in the KRT1 gene (F191C and K177N) and the other was in KRT10 (L453P) [1].
• Retinoid therapy is particularly effective in patients with KRT10 mutations possibly because they are less vulnerable to a down-regulation of K2e, potentially functioning as a substitute for the mutated protein in patients with KRT1 mutations [17].
• The coding region of KRT10 is 1707 bp and is comprised of eight exons [18].

Anatomical context of KRT10

• Semi-quantitative RT-PCR and western blot analysis demonstrated degradation of the KRT10 transcript, resulting in complete absence of keratin K10 protein in the epidermis and cultured keratinocytes of homozygous patients [19].
• The disease is caused by genetic defects of the epidermal keratin K1 or K10, leading to an impaired tonofilament network of differentiating epidermal cells [19].
• Blocking the synthesis of tissue-specific differentiation products, such as the K1 and K10 keratins designed to form extensive disulfide cross-links in cornified cells, or the assembly of uroplakin plaques allows epithelial cells to better migrate and proliferate, activities that are of overriding importance during wound repair [20].
• Abnormal keratin 1 and 10 cytoskeleton in cultured keratinocytes from epidermolytic hyperkeratosis caused by keratin 10 mutations [21].
• Poroid cells were heterogeneously stained with anti-CK7, CK8/18, CK 10/11 and CK19 antibodies, which reacted in the inner cells of dermal ducts and in the secretory cells of sweat glands [22].

Associations of KRT10 with chemical compounds

• Five out of 6 patients with KRT10 mutations benefited from treatment with oral acitretin (5-25mg/day) or topical tretinoin/tazarotene, but none of the patients with KRT1 mutations derived any benefit [17].
• The substitution of arginine (R) to histidine (H) at amino acid residue 156 (R156H) of coiled 1A region is one of the most frequent mutations of KRT10 [23].
• In the analogous region of type I keratin 10, an arginine-to-proline and an arginine-to-serine transition in codon 156 have been identified [24].
• In this report we identify a novel, single base pair substitution resulting in an amino acid exchange from tyrosine to serine at residue 14 within the conserved 1A region of K10 (Y14S) [25].
• These proteins were expressed mainly in the stratum spinosum and stratum granulosum, and their patterns of expression were almost the same as those of the CK1, CK10, and involucrin proteins [26].

Regulatory relationships of KRT10

• A distinct band of expression of cytokeratin 10 was seen in the upper stratum granulosum of control composites but only patchy expression was seen after transglutaminase expression [27].
• Because keratin 10 is the co-expressed partner of keratin 1, it was not surprising when abnormalities in keratin 10 were found in other families with EHK [28].
• The expression of p21WAF1/cip1 localized mostly to the upper half of the epithelium at early passage and was more intense in the HPV 16-positive UT-DEC-2 cell line expressing K10 [29].
• High-cell-density phorbol ester and retinoic acid upregulate involucrin and downregulate suprabasal keratin 10 in autocrine cultures of human epidermal keratinocytes [30].

Other interactions of KRT10

• However, homozygosity by descent was observed with the polymorphic probes KRT9, KRT10 Ava II, and D17S1787 in both affected children, consistent with a recessive defect in a type I keratin [31].
• Strong induction of the wound-healing keratins K6, K16 and K17 was found in the suprabasal epidermis, which are not able to compensate for the lack of keratin 10 [19].
• At the same time, K1/K10 mRNA and protein expression decreased dramatically, while the mRNA for D1 cyclin became detectable, and the cells became highly proliferative [32].
• In contrast, CK1 and CK10 were prominent markers of suprabasaloid differentiation stages and produced complementary stainings to those of CK5 and 14 [33].
• The NGFR gene and Hox-2 homeo box locus are localized distal to the 17q21 break point and thus distal to the K10 gene [34].

Analytical, diagnostic and therapeutic context of KRT10

• Sequence analysis revealed a homozygous nonsense mutation of the KRT10 gene in the affected family members, leading to a premature termination codon (p.Q434X), whereas the clinically unaffected consanguineous parents were both heterozygous carriers of the mutation [19].
• Quantitative real-time PCR indicated a significant decrease in KRT10 mRNA levels in affected dogs compared with wild-type dogs [2].
• KRT10 was localized to the on-going canine radiation hybrid map to chromosome 9 in the type I keratin gene cluster [18].
• We have determined the chromosomal location of the genes for the human keratin intermediate filament proteins K1 (type II; 67 kDa) and K10 (type I; 57 kDa) by the use of specific cDNA clones in conjunction with somatic cell hybrid analysis and in situ hybridization [34].
• Cytokeratin 10 molecules were shown by flow cytometry to be exposed on the surface of both desquamated nasal epithelial cells and keratinocytes [35].

References