Archives of Dermatological Research

, Volume 300, Issue 2, pp 81–85 | Cite as

Rapid detection of homozygous mutations in congenital recessive ichthyosis

  • Jennie Lugassy
  • Hans Christian Hennies
  • Margarita Indelman
  • Ziad Khamaysi
  • Reuven Bergman
  • Eli Sprecher
Original Paper

Abstract

Congenital recessive ichthyoses (CRI) form a remarkably heterogeneous group of diseases, resulting from mutations in at least eight distinct genes, six of which have been identified so far. In the present study we ascertained two CRI families of Iranian and Druze origins. Exploiting the high degree of consanguinity characterizing these populations, we typed all family members for microsatellite markers spanning the major CRI chromosomal loci and used homozygosity mapping to identify candidate genes for subsequent mutational analysis. This strategy led to the rapid identification of two novel homozygous CRI-causing mutations in TGM1 (c.2058delC) and FLJ39501 (p.W521X). The present data demonstrate that the molecular analyses of CRI in consanguineous families can be readily completed in less than 96 h at relatively low costs.

Keywords

Ichthyosis Mutation Homozygosity mapping 

References

  1. 1.
    Akiyama M, Sugiyama-Nakagiri Y, Sakai K, McMillan JR, Goto M, Arita K, et al. (2005) Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer. J Clin Invest 115:1777–1784PubMedCrossRefGoogle Scholar
  2. 2.
    Becker K, Csikos M, Sardy M, Szalai ZS, Horvath A, Karpati S (2003) Identification of two novel nonsense mutations in the transglutaminase 1 gene in a Hungarian patient with congenital ichthyosiform erythroderma. Exp Dermatol 12:324–329PubMedCrossRefGoogle Scholar
  3. 3.
    Brash AR, Yu Z, Boeglin WE, Schneider C (2007) The hepoxilin connection in the epidermis. FEBS J 274:3494–3502PubMedCrossRefGoogle Scholar
  4. 4.
    Eckl KM, Krieg P, Küster W, Traupe H, André F, Wittstruck N, Fürstenberger G, Hennies HC (2005) Mutation spectrum and functional analysis of epidermis-type lipoxygenases in patients with autosomal recessive congenital ichthyosis. Hum Mutat 2:351–61CrossRefGoogle Scholar
  5. 5.
    Fischer J, Faure A, Bouadjar B, Blanchet-Bardon C, Karaduman A, Thomas I, et al. (2000) Two new loci for autosomal recessive ichthyosis on chromosomes 3p21 and 19p12-q12 and evidence for further genetic heterogeneity. Am J Hum Genet 66:904–913PubMedCrossRefGoogle Scholar
  6. 6.
    Fürstenberger G, Epp N, Eckl KM, Hennies HC, Jørgensen C, Hallenborg P, Kristiansen K, Krieg P (2007) Role of epidermis-type lipoxygenases for skin barrier function and adipocyte differentiation. Prostaglandins Other Lipid Mediat 82:128–134PubMedCrossRefGoogle Scholar
  7. 7.
    Hatsell SJ, Stevens H, Jackson AP, Kelsell DP, Zvulunov A (2003) An autosomal recessive exfoliative ichthyosis with linkage to chromosome 12q13. Br J Dermatol 149:174–180PubMedCrossRefGoogle Scholar
  8. 8.
    Hennies HC, Kuster W, Wiebe V, Krebsova A, Reis A (1998) Genotype/phenotype correlation in autosomal recessive lamellar ichthyosis. Am J Hum Genet 62:1052–1061PubMedCrossRefGoogle Scholar
  9. 9.
    Huber M, Rettler I, Bernasconi K, Frenk E, Lavrijsen AP, Ponec M, Bon A, Lautenschlager S, Schorderet DF, Hohl D (1995) Mutations of keratinocyte transglutaminase in lamellar ichthyosis. Science 267:525–528PubMedCrossRefGoogle Scholar
  10. 10.
    Jobard F, Lefevre C, Karaduman A, Blanchet-Bardon C, Emre S, Weissenbach J, et al. (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 11:107–113PubMedCrossRefGoogle Scholar
  11. 11.
    Kelsell DP, Norgett EE, Unsworth H, Teh MT, Cullup T, Mein CA, et al. (2005) Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Am J Hum Genet 76:794–803PubMedCrossRefGoogle Scholar
  12. 12.
    Lefevre C, Jobard F, Caux F, Bouadjar B, Karaduman A, Heilig R, et al. (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 69:1002–1012PubMedCrossRefGoogle Scholar
  13. 13.
    Lefevre C, Audebert S, Jobard F, Bouadjar B, Lakhdar H, Boughdene-Stambouli O, et al. (2003) Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2. Hum Mol Genet 12:2369–2378PubMedCrossRefGoogle Scholar
  14. 14.
    Lefevre C, Bouadjar B, Karaduman A, Jobard F, Saker S, Ozguc M, et al. (2004) Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis. Hum Mol Genet 13:2473–2482PubMedCrossRefGoogle Scholar
  15. 15.
    Lefevre C, Bouadjar B, Ferrand V, Tadini G, Megarbane A, Lathrop M, et al. (2006) Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Hum Mol Genet 15:767–776PubMedCrossRefGoogle Scholar
  16. 16.
    Mizrachi-Koren M, Geiger D, Indelman M, Bitterman-Deutsch O, Bergman R, Sprecher E (2005) Identification of a novel locus associated with congenital recessive ichthyosis on 12p11.2-q13. J Invest Dermatol 125:456–462PubMedCrossRefGoogle Scholar
  17. 17.
    Mizrachi-Koren M, Shemer S, Morgan M, Indelman M, Khamaysi Z, Petronius D, et al. (2006) Homozygosity mapping as a screening tool for the molecular diagnosis of hereditary skin diseases in consanguineous populations. J Am Acad Dermatol 55:393–401PubMedCrossRefGoogle Scholar
  18. 18.
    Oji V, Traupe H (2006) Ichthyoses: differential diagnosis and molecular genetics. Eur J Dermatol 16:349–359PubMedGoogle Scholar
  19. 19.
    Raghunath M, Hennies HC, Velten F, Wiebe V, Steinert P, M Reis A Traupe H (1988) A novel in situ method for the detection of deficient transglutaminase activity in the skin. Arch Dermatol Res 290:621–627CrossRefGoogle Scholar
  20. 20.
    Rizzo WB (2007) Sjogren–Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metabol 90:1–9CrossRefGoogle Scholar
  21. 21.
    Russell LJ, DiGiovanna JJ, Rogers GR, Steinert PM, Hashem N, Compton JG, et al. (1995) Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis. Nat genet 9:279–283PubMedCrossRefGoogle Scholar
  22. 22.
    Sheffield VC, Nishimura DY, Stone EM (1995) Novel approaches to linkage mapping. Curr Opin Genet Dev 5:335–341PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jennie Lugassy
    • 1
    • 2
  • Hans Christian Hennies
    • 4
  • Margarita Indelman
    • 1
  • Ziad Khamaysi
    • 1
  • Reuven Bergman
    • 1
    • 2
  • Eli Sprecher
    • 1
    • 2
    • 3
  1. 1.Laboratory of Molecular Dermatology, Department of Dermatology, Rambam Health Care Campus Rambam Medical CenterHaifaIsrael
  2. 2.Faculty of MedicineRappaport Institute for Research in the Medical Sciences, Technion—Israel Institute of TechnologyHaifaIsrael
  3. 3.Center for Translational GeneticsRappaport Institute for Research in the Medical Sciences, Technion—Israel Institute of TechnologyHaifaIsrael
  4. 4.Division of Dermatogenetics, Cologne Center for GenomicsUniversity of CologneCologneGermany

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