title: The CYLD p.R758X worldwide recurrent nonsense mutation detected in patients with multiple familial trichoepithelioma type 1, Brooke-Spiegler syndrome and familial cylindromatosis represents a mutational hotspot in the gene.
abstract: 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.
authors: MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary. farkaskatalin88@gmail.com.
authors: Katalin
authors: K
authors: Farkas
authors: Department of Medical Genetics, University of Szeged, 4 Somogyi B., H-6720, Szeged, Hungary. kocsisd.barbi@gmail.com.
authors: Barbara Kocsis
authors: BK
authors: Deák
authors: Department of Dermatology and Venereology of Consorcio Hospital Universitario de Valencia, Valencia, Spain. laura_cubells@hotmail.com.
authors: Laura Cubells
authors: LC
authors: Sánchez
authors: Department of Dermatology and Venereology of Consorcio Hospital Universitario de Valencia, Valencia, Spain. anamercedes.victoria@hotmail.com.
authors: Ana Mercedes Victoria
authors: AM
authors: Martínez
authors: Department of Dermatology and Venereology of Consorcio Hospital Universitario de Valencia, Valencia, Spain. juan.j.vilata@uv.es.
authors: Juan José Vilata
authors: JJ
authors: Corell
authors: Genetics Laboratory of Clinical Analysis, Consorcio Hospital General Universitario de Valencia, Valencia, Spain. alfredomontorobotella@gmail.com.
authors: Alfredo Montoro
authors: AM
authors: Botella
authors: Genetics Laboratory of Clinical Analysis, Consorcio Hospital General Universitario de Valencia, Valencia, Spain. goimarcaida@gmail.com.
authors: Goitzane Marcaida
authors: GM
authors: Benito
authors: Genetics Laboratory of Clinical Analysis, Consorcio Hospital General Universitario de Valencia, Valencia, Spain. rodriguez_raqlop@gva.se.
authors: Raquel Rodríguez
authors: RR
authors: López
authors: Unit of Molecular Genetics, Bioptical Laboratory, Pilsen, Czech Republic. vanecek@medima.cz.
authors: Tomas
authors: T
authors: Vanecek
authors: The Sikl Department of Pathology, Charles University Medical Faculty Hospital, Medical Faculty in Pilsen, Charles University in Prague, Pilsen, Czech Republic. kazakov@medima.cz.
authors: Dmitry V
authors: DV
authors: Kazakov
authors: Department of Clinical Genetics, Erasmus MC, Rotterdam, Netherlands. j.kromosoeto@erasmusmc.nl.
authors: Joan N R
authors: JN
authors: Kromosoeto
authors: Department of Clinical Genetics, Erasmus MC, Rotterdam, Netherlands. a.vandenouweland@erasmusmc.nl.
authors: Ans M W
authors: AM
authors: van den Ouweland
authors: Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary. vargamed@t-online.hu.
authors: János
authors: J
authors: Varga
authors: MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary. szell.marta@med.u-szeged.hu.|Department of Medical Genetics, University of Szeged, 4 Somogyi B., H-6720, Szeged, Hungary. szell.marta@med.u-szeged.hu.
authors: Márta
authors: M
authors: Széll
authors: MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary. nikoletta.nagy@gmail.com.|Department of Medical Genetics, University of Szeged, 4 Somogyi B., H-6720, Szeged, Hungary. nikoletta.nagy@gmail.com.|Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary. nikoletta.nagy@gmail.com.
authors: Nikoletta
authors: N
authors: Nagy
mesh_terms: D001317:Austria; D018389:Codon, Nonsense; D000074749:Deubiquitinating Enzyme CYLD; D005260:Female; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis* / Q000235:genetics*; D009426:Netherlands; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D013030:Spain; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD