Abstract |
Dowling-Degos disease ( DDD) is an autosomal dominant genodermatosis characterized by progressive and disfiguring reticulate hyperpigmentation of the flexures. We performed a genomewide linkage analysis of two German families and mapped DDD to chromosome 12q, with a total LOD score of 4.42 ( theta =0.0) for marker D12S368. This region includes the keratin gene cluster, which we screened for mutations. We identified loss-of-function mutations in the keratin 5 gene (KRT5) in all affected family members and in six unrelated patients with DDD. These represent the first identified mutations that lead to haploinsufficiency in a keratin gene. The identification of loss-of-function mutations, along with the results from additional functional studies, suggest a crucial role for keratins in the organization of cell adhesion, melanosome uptake, organelle transport, and nuclear anchorage.
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Authors | Regina C Betz, Laura Planko, Sibylle Eigelshoven, Sandra Hanneken, Sandra M Pasternack, Heinrich Bussow, Kris Van Den Bogaert, Joerg Wenzel, Markus Braun-Falco, Arno Rutten, Michael A Rogers, Thomas Ruzicka, Markus M Nöthen, Thomas M Magin, Roland Kruse |
Journal | American journal of human genetics
(Am J Hum Genet)
Vol. 78
Issue 3
Pg. 510-9
(Mar 2006)
ISSN: 0002-9297 [Print] United States |
PMID | 16465624
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- KRT5 protein, human
- Keratin-5
- Keratins
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Topics |
- Base Sequence
- Biological Transport
- Cell Adhesion
(genetics)
- Chromosomes, Human, Pair 12
(genetics)
- Epidermolysis Bullosa Simplex
(genetics, pathology)
- Female
- Haploidy
- Humans
- Keratin-5
- Keratins
(analysis, genetics)
- Male
- Melanosomes
(metabolism)
- Molecular Sequence Data
- Mutation, Missense
- Organelles
(metabolism)
- Pedigree
- Skin
(chemistry, pathology)
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