BACKGROUND: Multiple familial trichoepithelioma type 1 (MFT1; MIM 601606), a rare monogenic skin disease with autosomal dominant inheritance, is characterized by the development of multiple skin-colored papules on the central area of the face, frequently occurring in the nasolabial area. The disease is associated with various mutations in the cylindromatosis (CYLD; MIM 605018) gene that are also responsible for familial cylindromatosis (FC) and Brooke-Spiegler syndrome (BSS). METHODS: Recently we have identified a Spanish MFT1 pedigree with two affected family members (father and daughter). Direct sequencing of the CYLD gene revealed a worldwide recurrent heterozygous nonsense mutation (c.2272C/T, p.R758X) in the patients. RESULTS: This mutation has already been detected in patients with all three clinical variants - BSS, FC and MFT1 - of the CYLD-mutation spectrum. Haplotype analysis was performed for the Spanish patients with MFT1, Dutch patients with FC and an Austrian patient with BSS, all of whom carry the same heterozygous nonsense p.R758X CYLD mutation. CONCLUSIONS: Our results indicate that this position is a mutational hotspot on the gene and that patients carrying the mutation exhibit high phenotypic diversity.

Department of Clinical Genetics Erasmus MC Rotterdam Netherlands

Department of Dermatology and Allergology University of Szeged Szeged Hungary

Department of Dermatology and Venereology of Consorcio Hospital Universitario de Valencia Valencia Spain

Department of Medical Genetics University of Szeged 4 Somogyi B H 6720 Szeged Hungary

Genetics Laboratory of Clinical Analysis Consorcio Hospital General Universitario de Valencia Valencia Spain

MTA SZTE Dermatological Research Group University of Szeged Szeged Hungary

The Sikl Department of Pathology Charles University Medical Faculty Hospital Medical Faculty in Pilsen Charles University Prague Pilsen Czech Republic

Unit of Molecular Genetics Bioptical Laboratory Pilsen Czech Republic

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