A homozygous nonsense mutation in the 3 chain gene of laminin 5 (LAMA3) in lethal (Herlitz) junctional epidermolysis bullosa
| Autor: | S. Kivirikko, J. A. McGrath, C. Baudoin, D. Aberdam, S. Ciatti, M. G. S. Dunnill, J. R. McMillan, R. A. J. Eady, J.-P. Ortonne, G. Meneguzzi, J. Ultto, A. M. Christiano |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Male
Candidate gene Molecular Sequence Data Nonsense mutation medicine.disease_cause Polymerase Chain Reaction Laminin Genetics medicine Humans Point Mutation Molecular Biology Genetics (clinical) DNA Primers Mutation Base Sequence integumentary system biology Hemidesmosome Point mutation Homozygote Infant General Medicine medicine.disease Pedigree Phenotype biology.protein Female Epidermolysis bullosa Epidermolysis Bullosa Junctional Cell Adhesion Molecules Junctional epidermolysis bullosa (veterinary medicine) |
| Zdroj: | Human Molecular Genetics. 4:959-962 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/4.5.959 |
| Popis: | The inherited mechanobullous disorder, junctional epidermolysis bullosa (JEB), is characterized by extensive blistering and erosions of the skin and mucous membranes. The diagnostic hallmarks of JEB include ultrastructural abnormalities in the hemidesmosomes of the cutaneous basement membrane zone, as well as an absence of staining with antibodies against the anchoring filament protein, laminin 5. Therefore, the three genes encoding alpha 3, beta 3 and gamma 2 chains of laminin 5, known as LAMA3, LAMB3 and LAMC2, are candidate genes for JEB. We have previously demonstrated mutations in the LAMB3 and LAMC2 genes in several families with JEB. We initiated mutation analysis from an affected child by PCR amplification of individual LAMA3 exons, followed by heteroduplex analysis. Nucleotide sequencing of heteroduplexes identified a homozygous nonsense mutation within domain I/II of the alpha 3 chain. These findings provide the first evidence that nonsense mutations within the LAMA3 gene are also involved in the pathogenesis of JEB, and indicate that mutations of all three genes of laminin 5 can result in the JEB phenotype. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|