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Structural changes in epidermal scale and appendages as indicators of defective TGM1 activity

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Abstract

Defective transglutaminase 1 (TGM1) is a causative factor in some cases of lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE) despite large differences in the phenotype between these conditions. In some of these individuals, defective cornified envelopes (CEs) have been reported by light or electron microscopic examination in epidermal scale, nail and/or hair. These findings suggest that assessment of such defects could have a diagnostic utility in distinguishing TG1-deficient versus non-deficient cases of autosomal recessive ichthyosis (ARI) . Present work (a) examines the integrity of CEs in epidermal scale and appendages in a case of TGM1-deficient CIE, (b) assesses the utility of hair/nail versus scale analysis in the diagnosis of TGM1 deficiency in vivo and (c) helps characterize the consequences of the V518M mutation in TGM1, about which conflicting reports have appeared. To this end, epidermal scale or callus, nail and hair samples from a patient with TGM1-deficient CIE, his asymptomatic family members and control subjects were extracted vigorously in sodium dodecyl sulfate and dithiothreitol and examined by light (phase contrast) and electron microscopy. Both epidermal scale and nail from the index case lacked the prominent cell borders that were visible by phase contrast microscopy after detergent extraction of control samples. (By contrast, abundant envelope structures were visible in extracted epidermal scale from patients with ichthyosis vulgaris, loricrin keratoderma and epidermolytic hyperkeratosis.) Electron microscopy confirmed the paucity of intact CEs, and revealed further that hair cuticle cells from the same subject also lacked the marginal bands that are visible in control hair samples. Such aberrations were evident neither in the samples from asymptomatic relatives of the index case nor in the hair-cuticle cells of numerous normal individuals, evidence that this defect is not a common polymorphism. These studies extend our prior work on TGM1-deficient LI to the full spectrum of TGM1-deficient patients, showing that the CIE phenotype, when attributable to a V518M heterozygous mutation in TGM1 in combination with an inactive allele, confers a cross-linking deficiency in a variety of keratinizing epithelia, as previously shown for TGM1-negative LI. These results further suggest that a non-invasive assessment of scale, nail and hair could be of diagnostic utility in distinguishing patients across a full range of phenotypes with deficiency in TGM1-encoded transglutaminase activity from other causes of ARI.

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References

  1. Akiyama M, Sawamura D, Shimizu H (2003) The clinical spectrum of nonbullous congenital ichthyosiform erythroderma and lamellar ichthyosis. Clin Exp Dermatol 28:235–240

    Article  PubMed  CAS  Google Scholar 

  2. Bitoun E, Micheloni A, Lamant L, Bonnart C, Tartaglia-Polcini A, Cobbold C, Al Saati T, Mariotti F, Mazereeuw-Hautier J, Boralevi F, Hohl D, Harper J, Bodemer C, D’Alessio M, Hovnanian A (2003) LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome. Hum Molec Genet 12:2417–2430

    Article  PubMed  CAS  Google Scholar 

  3. Choate KA, Williams ML, Khavari PA (1998) Abnormal transglutaminase 1 expression pattern in a subset of patients with erythrodermic autosomal recessive ichthyosis. J Invest Dermatol 110:8–12

    Article  PubMed  CAS  Google Scholar 

  4. Cserhalmi-Friedman PB, M ML, Christiano AM (2001) Diagnosis of autosomal recessive lamellar ichthyosis with mutations in the TGM1 gene. Br J Dermatol 144:726–730

    Article  PubMed  CAS  Google Scholar 

  5. DiGiovanna JJ, Robinson-Bostom L (2003) Ichthyosis. Etiology, diagnosis, and management. Am J Clin Dermatol 4:81–95

    Article  PubMed  Google Scholar 

  6. Elias PM, Schmuth M, Uchida Y, Rice RH, Behne M, Crumrine D, Feingold KR, Holleran WM, Pharm D (2002) Basis for permeability barrier abnormality in lamellar ichthyosis. Exp Dermatol 11:248–256

    Article  PubMed  Google Scholar 

  7. Esposito G, Auricchio L, Rescigno G, Paparo F, Rinaldi M, Salvatore F (2001) Transglutaminase 1 gene mutations in Italian patients with autosomal recessive lamellar ichthyosis. J Invest Dermatol 116:809–812

    Article  PubMed  CAS  Google Scholar 

  8. Fartasch M, Williams ML, Elias PM (1999) Altered lamellar body secretion and stratum corneum membrane structure in Netherton syndrome. Arch Dermatol 135:823

    Article  PubMed  CAS  Google Scholar 

  9. Ghadially R, Williams ML, Hou SYE, Elias PM (1992) Membrane structural abnormalities in the stratum corneum of the autosomal recessive ichthyoses. J Invest Dermatol 99:755–763

    Article  PubMed  CAS  Google Scholar 

  10. Hennies HC, Kuster W, Wiebe V, Krebsova A, A R (1998) Genotype/phenotype correlation in autosomal recessive lamellar ichthyosis. Am J Hum Genet 62:1052–1061

    Article  PubMed  CAS  Google Scholar 

  11. Hohl D, Aeschlimann D, Huber M (1998) In vitro and rapid in situ transglutaminase assays for congenital ichthyoses - a comparative study. J Invest Dermatol 110:268–271

    Article  PubMed  CAS  Google Scholar 

  12. Huber M, Rettler I, Bernasconi K, Frenk E, Lavrijsen SPM, Ponec M, Bon A, Lautenschlager S, Schorderet DF, Hohl D (1995) Mutations of keratinocyte transglutaminase in lamellar ichthyosis. Science 267:525–528

    Article  PubMed  CAS  Google Scholar 

  13. Itin PH, Sarasin A, Pittelkow MR (2001) Trichothiodystrophy: update on the sulfur-deficient brittle hair syndromes. J Am Acad Dermatol 44:891–920

    Article  PubMed  CAS  Google Scholar 

  14. Jeon S, Djian P, Green H (1998) Inability of keratinocytes lacking their specific transglutaminase to form cross-linked envelopes: Absence of envelopes as a simple diagnostic test for lamellar ichthyosis. Proc Natl Acad Sci USA 95:687–690

    Article  PubMed  CAS  Google Scholar 

  15. Jessen BA, Qin Q, Phillips MA, Phillips DL, Rice RH (2001) Keratinocyte differentiation marker suppression by arsenic: Mediation by AP1 response elements and antagonism by tetradecanoylphorbol acetate. Toxicol Appl Pharmacol 174:302–311

    Article  PubMed  CAS  Google Scholar 

  16. Jobard F, Lefèvre C, Karaduman A, Blanchet-Bardon C, Emre S, Weissenbach J, Özgüc M, Lathrop M, Prud’homme J-F, Fischer J (2002) Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1. Hum Mol Genet 11:107–113

    Article  PubMed  CAS  Google Scholar 

  17. Laiho E, Ignatius J, Mikkola H, Yee VC, Teller DC, Niemi K-M, Saarialho-Kere U, Kere J, Palotie A (1997) Transglutaminase 1 mutations in autosomal recessive congenital ichthyosis: Private and recurrent mutations in an isolated population. Am J Hum Genet 61:529–538

    Article  PubMed  CAS  Google Scholar 

  18. Lefevre C, Jobard F, Caux F, Bouadjar B, Karaduman A, Heilig R, Lakhdar H, Wollenberg A, Verret JL, Weissenbach J, Ozguc M, Lathrop M, Prud’homme JF, Fischer J (2001) Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome. Am J Hum Genet 69:1002–1012

    Article  PubMed  CAS  Google Scholar 

  19. Lichti U (1991) Hair follicle translgutaminases. Ann N Y Acad Sci 642:82–98

    Article  PubMed  CAS  Google Scholar 

  20. Nemes Z, Demeny M, Marekov LN, Fesus L, Steinert PM (2000) Cholesterol 3-sulfate interferes with cornified envelope assembly by diverting transglutaminase 1 activity from the formation of cross-links and esters to the hydrolysis of glutamine. J Biol Chem 275:2636–2646

    Article  PubMed  CAS  Google Scholar 

  21. Nemes Z, Marekov LN, Fesus L, Steinert PM (1999) A novel function for transglutaminase 1: Attachment of long-chain omega-hydroxyceramides to involucrin by ester bond formation. Proc Natl Acad Sci USA 96:8402–8407

    Article  PubMed  CAS  Google Scholar 

  22. Rice RH, Crumrine D, Hohl D, Munro CS, Elias PM (2003) Cross-linked envelopes in nail plate in lamellar ichthyosis. Br J Dermatol 149:1050–1054

    Article  PubMed  CAS  Google Scholar 

  23. Rice RH, Wong VJ, Price VH, Hohl D, Pinkerton KE (1996) Cuticle cell defects in lamellar ichthyosis hair and anomalous hair shaft syndromes visualized after detergent extraction. Anatomic Rec 246:433–440

    Article  CAS  Google Scholar 

  24. Rice RH, Wong VJ, Williams ML, Price VH, Hohl D, Sundberg JP, Pinkerton KE (1999) Hair shaft defects visualized after detergent extraction. Exp Dermatol 8:308–310

    PubMed  CAS  Google Scholar 

  25. Rodushkin L, Axelsson MD (2003) Application of double focusing sector field ICP-MS for multielemental characterization of human hair and nails. Part III. Direct analysis by laser ablation. Sci Total Environ 305:23–39

    Article  PubMed  CAS  Google Scholar 

  26. Russell LJ, DiGiovanna JJ, Rogers GR, Steinert PM, Hashem N, Compton JG, Bale SJ (1995) Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis. Nat Genet 9:279–283

    Article  PubMed  CAS  Google Scholar 

  27. Tian D, Ma H, Feng Z, Xia Y, Le XC, Ni Z, Allen J, Collins B, Schreinemachers D, Mumford JL (2001) Analyses of micronuclei in exfoliated epithelial cells from individuals chronically exposed to arsenic via drinking water in Inner Mongolia, China. J Toxicol Environ Health 64:473–484

    Article  CAS  Google Scholar 

  28. Williams ML, Elias PM (1985) Heterogeneity in autosomal recessive ichthyosis: Clinical and biochemical differentiation of lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma. Arch Dermatol 121:477–488

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Judy L. Mumford (USEPA) for generously providing hair from arsenic-exposed individuals, Dr. Matthias Schmuth for providing ichthyosis samples, Michelle A. Gras (UC Davis Interdisciplinary Center for Plasma Mass Spectrometry) for arsenic measurements, Michael R. Dunlap, Felix R. Li and Heather Weitman for assistance in collecting and processing samples of hair from normal donors and arsenic-exposed individuals and especially the patient and family members for their cooperation. This work was supported by US Public Health Service grants AR27130, ES04699 and ES05707.

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Authors and Affiliations

  1. Department of Environmental Toxicology, University of California, One Shields Avenue, Davis, CA, 95616-8588, USA

    Robert H. Rice

  2. Dermatology Service, Veterans Affairs Medical Center, Department of Dermatology, University of California, San Francisco, CA, USA

    Debra Crumrine, Yoshikazu Uchida & Peter M. Elias

  3. Department of Dermatology, Medical University Innsbruck, Anichstrasse 35, A-6020, Innsbruck, Austria

    Robert Gruber

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  1. Robert H. Rice
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Correspondence to Robert H. Rice.

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Rice, R.H., Crumrine, D., Uchida, Y. et al. Structural changes in epidermal scale and appendages as indicators of defective TGM1 activity. Arch Dermatol Res 297, 127–133 (2005). https://doi.org/10.1007/s00403-005-0591-7

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  • DOI: https://doi.org/10.1007/s00403-005-0591-7

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