Buschke-Ollendorff syndrome in a three-generation family: influence of a novel LEMD3 mutation to tropoelastin expression

Buschke-Ollendorff syndrome refers to the concomitant occurrence of connective tissue nevi, composed of elastic fibers in most cases, with osteopoikilosis. This autosomal dominant inherited disorder is caused by mutations in the gene LEMD3 on chromosome 12q14, which induces a rather heterogeneous clinical phenotype. Here, we report on the most proximal germline mutation found to date in the LEMD3 gene, p.Val94fs, in a three-generation Swiss family. Quantitative RNA analyses in affected and non-affected skin tissue from the proband demonstrate a comparable nonsense-mediated decay of mutant LEMD3 mRNA in both tissues; however, different levels of tropoelastin expression suggest that additional factors are involved in the development of the cutaneous lesions.