Disease relevance of Ichthyosis, Lamellar

• Treatment of lamellar ichthyosis and other keratinising dermatoses with an oral synthetic retinoid [1].
• In contrast, in normoproliferative monogenic disorders of keratinization (X-linked recessive ichthyosis, autosomal dominant ichthyosis vulgaris, non-erythrodermic lamellar ichthyosis), no increase in tenascin expression was found compared with normal skin [2].
• We have regenerated skin from transglutaminase 1 (TGase1)-deficient patients with the genetic skin disease lamellar ichthyosis (LI) on nude mice to examine the corrective impact of direct naked plasmid injection [3].
• Strong founder effect for a transglutaminase 1 gene mutation in lamellar ichthyosis and congenital ichthyosiform erythroderma from Norway [4].
• Patients with non-erythrodermic lamellar ichthyosis showed a marked decrease in levels of the important acylceramide, ceramide 1, whereas those with other types of autosomal recessive ichthyosis (limited lamellar ichthyosis and non-bullous ichthyosiform erythroderma) had mean levels similar to the controls [5].

High impact information on Ichthyosis, Lamellar

• We recently mapped the disease locus for severe autosomal recessive lamellar ichthyosis (LI) to chromosome 14q11 and showed complete linkage with TGM1, the gene encoding transglutaminase 1 [6].
• Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer [7].
• Harlequin ichthyosis (HI)--the most severe form of keratinizing disorders, often lethal in the neonatal period--is characterized by a profound thickening of the keratin skin layer, a dense "armor"-like scale that covers the body, and contraction abnormalities of the eyes, ears, and mouth [8].
• Topical N-acetylcysteine for lamellar ichthyosis [9].
• Deficient cross-linking of the cell envelope in some patients with the autosomal recessive skin disorder lamellar ichthyosis (LI) and several mutations of the TGase 1 gene that have been identified in families with LI suggest the importance of this gene in production of the cell envelope [10].

Chemical compound and disease context of Ichthyosis, Lamellar

• Utilizing gas chromatography, we found that the cholesterol sulfate concentration was less than 350 micrograms/100 ml plasma in 9 normal adults, 2 subjects with ichthyosis vulgaris and 2 subjects with lamellar ichthyosis [11].
• The dichotomy with respect to the response to acitretin suggests that lamellar ichthyosis is a spectrum of at least two conditions [12].
• Topical application of tazarotene in the treatment of nonerythrodermic lamellar ichthyosis [13].
• Cyclosporine in lamellar ichthyosis [14].
• A multicenter study of the effectiveness of 13-cis-retinoic acid (isotretinoin) in lamellar ichthyosis and epidermolytic hyperkeratosis has been conducted [15].

Biological context of Ichthyosis, Lamellar

• These data suggest that defects in TGK cause lamellar ichthyosis and that intact cross-linkage of cornified cell envelopes is required for epidermal tissue homeostasis [16].
• Autosomal recessive lamellar ichthyosis: identification of a new mutation in transglutaminase 1 and evidence for genetic heterogeneity [17].
• Thus the lamellar ichthyosis phenotype in this case is likely attributable to a novel non-sense mutation in the coding region leading to reduced transglutaminase 1 mRNA levels rather than mutation of the Sp1 site [18].
• Our findings demonstrate that mutations of both alleles of the transglutaminase 1 gene are the cause of lamellar ichthyosis in this family, and illustrate an emerging clinical application of molecular genetics in dermatology [19].
• In a cohort of four small families with lamellar ichthyosis we found confirmatory evidence for linkage (p < or = 0.01) to D14S275, a microsatellite marker close to transglutaminase 1 on chromosome 14q11 [19].

Anatomical context of Ichthyosis, Lamellar

• Recently, mutations have been identified in patients with lamellar ichthyosis in the TGM1 gene coding for keratinocyte transglutaminase, and a second locus has been mapped to chromosome 2 [20].
• Previously reported features of harlequin ichthyosis, such as the presence of giant mitochondria and an abnormal formation of the marginal band in luminal villi of acrosyringeal eccrine duct, were absent in our case [21].
• Bleomycin-induced chromosome aberrations in lymphocytes derived from patients with lamellar ichthyosis [22].

Gene context of Ichthyosis, Lamellar

• Stratum corneum morphology in cathepsin D-deficient mice was impaired, with increased numbers of corneocyte layers and faint staining of the cornified envelope only, which is similar to the human skin disease lamellar ichthyosis [23].
• The human cystatin M/E gene (CST6): exclusion candidate gene for harlequin ichthyosis [24].
• Finally, since the dual abnormalities in the lamellar body secretory system and filaggrin processing resemble two key features of human Harlequin ichthyosis, Pig-a null mice could provide an appropriate analog for further studies of this disease [25].
• Defects in cross-linking of loricrin are detected in transglutaminase 1 knockout mice, the animal model of lamellar ichthyosis [26].
• Identification and characterization of a novel ABCA subfamily member, ABCA12, located in the lamellar ichthyosis region on 2q34 [27].

Analytical, diagnostic and therapeutic context of Ichthyosis, Lamellar

• Further studies of the epidermal lipid composition, and of possible mutations of the keratinocyte transglutaminase gene performed on epidermal cell cultures of harlequin ichthyosis, will be necessary before type II harlequin ichthyosis can be accepted as an extremely severe form of NBCIE [28].

References