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Genomics-Based Treatment in a Patient With Two Overlapping Heritable Skin Disorders: Epidermolysis Bullosa and Acrodermatitis Enteropathica Publisher Pubmed



Vahidnezhad H1, 2 ; Youssefian L1 ; Sotoudeh S3 ; Liu L4 ; Guy A4 ; Lovell PA4 ; Kariminejad A5 ; Zeinali S2 ; Mcgrath JA6 ; Uitto J1
Authors
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Authors Affiliations
  1. 1. Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, United States
  2. 2. Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
  3. 3. Department of Dermatology, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Viapath, St. Thomas' Hospital, London, United Kingdom
  5. 5. Clinical Genetics Deaprtment, Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran
  6. 6. St. John's Institute of Dermatology, King's College London (Guy's Campus), London, United Kingdom

Source: Human Mutation Published:2020


Abstract

Next-generation sequencing (NGS) is helpful in diagnosing complex genetic disorders and phenotypes, particularly when more than one overlapping condition is present. From a large cohort of 362 families with clinical manifestations of skin and mucosal fragility, referred by several major medical centers, one patient was found by NGS to have two overlapping heritable skin diseases, recessive dystrophic epidermolysis bullosa (RDEB; COL7A1 mutations) and acrodermatitis enteropathica (AE; SLC39A4 mutations). The pathogenicity of the variants was studied at gene expression as well as ultrastructural and tissue levels. Although there is no specific treatment for RDEB except avoiding trauma, supplementation with oral zinc (3 mg·kg−1·day−1) for the AE resulted in rapid amelioration of the skin findings. This case demonstrates the power of NGS in identifying two genetically unlinked diseases that led to effective treatment with major clinical benefits as an example of genomics-guided treatment. © 2020 Wiley Periodicals, Inc.
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