Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin blistering condition caused by mutations in the gene coding for collagen type VII. Genetically engineered RDEB dog keratinocytes were used to generate autologous epidermal sheets subsequently grafted on two RDEB dogs carrying a homozygous missense mutation in the col7a1 gene and expressing baseline amounts of the aberrant protein. Transplanted cells regenerated a differentiated and vascularized auto-renewing epidermis progressively repopulated by dendritic cells and melanocytes. No adverse immune reaction was detected in either dog. In dog 1, the grafted epidermis firmly adhered to the dermis throughout the 24-month follow-up, which correlated with efficient transduction (100%) of highly clonogenic epithelial cells and sustained transgene expression. In dog 2, less efficient (65%) transduction of primary keratinocytes resulted in a loss of the transplanted epidermis and graft blistering 5 months after transplantation. These data provide the proof of principle for ex vivo gene therapy of RDEB patients with missense mutations in collagen type VII by engraftment of the reconstructed epidermis, and demonstrate that highly efficient transduction of epidermal stem cells is crucial for successful gene therapy of inherited skin diseases in which correction of the genetic defect confers no major selective advantage in cell culture.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1038/jid.2011.172 | DOI Listing |
Br J Dermatol
January 2025
Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder due to pathogenic variants in the COL7A1 gene. In this study we determined the association between different categories of COL7A1 variants and clinical disease severity in 236 RDEB patients in North America. Published reports or in-silico predictions were used to assess the impact of pathogenic variants in COL7A1 on type VII collagen (C7) protein function.
View Article and Find Full Text PDFJ Dermatol
December 2024
Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Phasing, the process of determining which alleles at different loci on homologous chromosomes belong together on the same chromosome, is crucial in the diagnosis and management of autosomal recessive diseases. Advances in long-read sequencing technologies have significantly enhanced our ability to accurately determine haplotypes. This review discusses the application of low-coverage long-read sequencing, nanopore Cas9-guided long-read sequencing, and adaptive sampling in phasing, highlighting their utility in complex clinical scenarios.
View Article and Find Full Text PDFBMC Oral Health
December 2024
Department of Cranio-Maxillofacial Surgery, University Hospital Münster, Münster, Germany.
Background: Inherited epidermolysis bullosa (EB) is a genetic disorder characterized by skin fragility and unique oral features. This prospective study aimed to analyze the correlation between oral health-related quality of life (OHRQoL) and the objectively measured oral health indices of people suffering from EB and within their subtypes.
Methods: The German version of the Oral Health Impact Profile (OHIP-14G) was employed for the assessment of OHRQoL.
Indian J Dermatol
October 2024
Department of Dermatology, AFMC, Pune, Maharashtra, India E-mail:
Ann Med Surg (Lond)
December 2024
Nepal Medical College and Teaching Hospital, Kathmandu, Nepal.
Introduction: Bart syndrome is a rare genetic disorder characterized by epidermolysis bullosa (EB), aplasia cutis congenita, that is congenital local absence of skin and nail abnormalities.
Case Presentation: The authors herein, present a case of a 14-year-old boy with Bart syndrome. The syndrome was diagnosed clinically.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!