Loss-of-function mutations in the keratin 5 gene lead to Dowling-Degos disease.
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Betz RC, Planko L, Eigelshoven S, Hanneken S, Pasternack SM, Bussow H, Van Den Bogaert K, Wenzel J, Braun-Falco M, Rutten A, Rogers MA, Ruzicka T, Nothen MM, Magin TM, Kruse R
Loss-of-function mutations in the keratin 5 gene lead to Dowling-Degos disease.
Am J Hum Genet. 2006 Mar;78(3):510-9. Epub 2006 Jan 19.
- PubMed ID
- 16465624 [ View in PubMed]
- 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.