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A molecular defect in loricrin, the major component of the cornified cell envelope, underlies Vohwinkel's syndrome

Nature Genetics volume 13, pages 70–77 (1996)Cite this article

Abstract

Terminal keratinocyte differentiation involves coordinated expression of several functionally interdependent genes, many of which have been mapped to the epidermal differentiation complex (EDC) on chromosome 1q21. We have identified linkage of Vohwinkel's syndrome in an extended pedigree to markers flanking the EDC region with a maximum multipoint lod score of 14.3. Sequencing of the loricrin gene revealed an insertion that shifts the translation frame of the C-terminal Gly– and Gln/Lys–rich domains, and is likely to impair cornification. Our findings provide the first evidence for a defect in an EDC gene in human disease, and disclose novel insights into perturbations of cornified cell envelope formation.

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Author information

Author notes

  1. John A. McGrath

    Present address: St. John's Institute of Dermatology, St. Thomas's Hospital, London, UK

  2. Angela M. Christiano

    Present address: Department of Dermatology, Columbia University, College of Physicians and Surgeons, New York, New York, USA

Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX37BN, UK

    Elena Maestrini, Anthony P. Monaco, Alain Hovnanian, Daniel E. Weeks & Mark Lathrop

  2. Department of Human Genetics, University of Pittsburgh, Pennsylvania, 15261, USA

    Daniel E. Weeks

  3. Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania, 19107, USA

    John A. McGrath, Jouni Uitto & Angela M. Christiano

  4. Department of Dermatology, Asahikawa Medical College, Asahikawa, Japan

    Akemi Ishida-Yamamoto

  5. Department of Dermatology, The Cleveland Clinic Foundation, Cleveland, Ohio, 44106, USA

    Charles Camisa

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Maestrini, E., Monaco, A., McGrath, J. et al. A molecular defect in loricrin, the major component of the cornified cell envelope, underlies Vohwinkel's syndrome. Nat Genet 13, 70–77 (1996). https://doi.org/10.1038/ng0596-70

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