Disease relevance of Ichthyosis

• In addition to xeroderma pigmentosum, mutations in the human XPG gene cause early onset Cockayne syndrome (CS) [1].
• Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin [2].
• A cancer cell line selected for resistance to Et743 had chromosome alterations in a region that included the gene implicated in the hereditary disease xeroderma pigmentosum (XPG, also known as Ercc5) [3].
• ABCA3 is involved in lipid secretion via LGs from alveolar type II cells, and missense mutations in ABCA12 have been reported to cause lamellar ichthyosis type 2, a milder form of ichthyosis [4].
• Association between INK4a-ARF and p53 mutations in skin carcinomas of xeroderma pigmentosum patients [5].

Psychiatry related information on Ichthyosis

• Meiotic studies were undertaken in a 24-year-old male patient with short stature, chondrodysplasia punctata, ichthyosis, steroid sulfatase deficiency, and mild mental retardation with an inherited cytologically visible deletion of distal Xp [6].

High impact information on Ichthyosis

• The xeroderma pigmentosum group C (XPC) protein complex plays a key role in recognizing DNA damage throughout the genome for mammalian nucleotide excision repair (NER) [7].
• Telomere loss in these mice was mediated by XPF, a structure-specific nuclease involved in ultraviolet-induced damage repair and mutated in individuals with xeroderma pigmentosum [8].
• Different mutations in XPD give rise to three ultraviolet-sensitive syndromes: the skin cancer-prone disorder xeroderma pigmentosum (XP), in which repair of ultraviolet damage is affected; and the severe neurodevelopmental conditions Cockayne syndrome (CS) and trichothiodystrophy (TTD) [9].
• The xeroderma pigmentosum group D (XPD) helicase subunit of TFIIH functions in DNA repair and transcription initiation [9].
• In humans, mutations in the yeast RAD30 counterpart, POLH, cause the variant form of xeroderma pigmentosum (XP-V), and XP-V individuals suffer from a high incidence of sunlight-induced skin cancers [10].

Chemical compound and disease context of Ichthyosis

• In the human there is an X-linked gene affecting steroid sulphatase (STS) activity which, when deficient, is associated with X-linked congenital ichthyosis [11].
• Synergistic effect of caffeine on the cytotoxicity of ultraviolet irradiation and of hydrocarbon epoxides in strains of Xeroderma pigmentosum [12].
• Excision of thymine dimers from specifically incised DNA by extracts of xeroderma pigmentosum cells [13].
• Transformation of tissue-cultured xeroderma pigmentosum fibroblasts by treatment with N-methyl-N'-nitro-N-nitrosoguanidine [14].
• Removal of O6-methylguanine from DNA of normal and xeroderma pigmentosum-derived lymphoblastoid lines [15].

Biological context of Ichthyosis

• We conclude that the XPA-deficient mice strongly mimic the phenotype of humans with xeroderma pigmentosum [16].
• This latter phenotype was observed previously with a mutation in the SSL2 suppressor gene, which encodes the yeast homolog of the human gene ERCC-3, for which a defective form causes xeroderma pigmentosum [17].
• To identify DNA polymerases that are involved in Ig gene conversion, we created DT40 clones deficient in DNA polymerase eta (poleta), which, in humans, is defective in the variant form of xeroderma pigmentosum (XP-V) [18].
• Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis [19].
• The heritable DNA repair defect in human Xeroderma D cells, which results in failure to incise at u.v. light-induced pyrimidine dimers, has been partially but stably corrected by transfection of immortalised cells with the denV pyrimidine dimer glycosylase gene of bacteriophage T4 [20].

Anatomical context of Ichthyosis

• Oxygens in DNA are main targets for ethylnitrosourea in normal and xeroderma pigmentosum fibroblasts and fetal rat brain cells [21].
• To determine whether DNA polymerase eta plays a role in the hypermutation of immunoglobulin variable genes, we examined the frequency and pattern of substitutions in variable VH6 genes from the peripheral blood lymphocytes of three patients with xeroderma pigmentosum variant disease, whose polymerase eta had genetic defects [22].
• Restoration of u.v.-induced excision repair in Xeroderma D cells transfected with the denV gene of bacteriophage T4 [20].
• Cells cultured from most patients suffering from the sunlight-sensitive hereditary disorder xeroderma pigmentosum are defective in the ability to excise ultraviolet light (UV)-induced pyrimidine dimers from their DNA [23].
• Repair-deficient human cells from xeroderma pigmentosum complementation group C (XPC) are similar to the CHO cells in overall repair levels, but they are extremely sensitive to killing by UV irradiation [24].

Gene context of Ichthyosis

• Human cell extracts were fractionated to locate active components, including xeroderma pigmentosum (XP) and ERCC factors [25].
• SSL2 protein is 54% identical to the protein encoded by the human gene, ERCC-3, for which a defective form causes xeroderma pigmentosum and Cockayne's syndrome [26].
• One (RAD30A/POLH) has previously been characterized and shown to be defective in humans with the Xeroderma pigmentosum variant phenotype [27].
• The dysfunction of TFIIH could result in a large panel of genetic disorders, such as xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy [28].
• Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23 [29].

Analytical, diagnostic and therapeutic context of Ichthyosis

• The effect on the rate of sister chromatid exchanges (SCEs) in Bloom syndrome fibroblasts by cocultivation with Fanconi anemia and xeroderma pigmentosum fibroblasts and with Bloom syndrome heterozygotes was studied [30].
• Microinjection of the restriction endonuclease HaeIII, which causes DNA double-strand breaks with blunt ends, induces nuclear accumulation of p53 protein in normal and xeroderma pigmentosum (XP) primary fibroblasts [31].
• To address this question, we studied repair of MNU-induced N-methylpurines in the mitochondrial DNA from xeroderma pigmentosum complementation group D (XP-D) cells using quantitative Southern blot analysis and 32P-end-labeling techniques [32].
• Sequence analysis revealed the presence of mutations in the K2e gene in patients with ichthyosis bullosa of Siemens [33].
• Similar differences were detected for cisplatin repair-deficient Xeroderma pigmentosum cells treated in cell culture, indicating that in vivo/in vitro preferences for adduct site formation are not the result of DNA repair in vivo [34].

References