Multiple familial trichoepithelioma caused by mutations in the cylindromatosis tumor suppressor gene.
The recessive oncogene cylindromatosis (CYLD) mapping on 16q12-q13 is generally implicated in familial cylindromatosis, whereas a gene region for multiple familial trichoepithelioma has been assigned to 9p21. Markers from both chromosome intervals were subjected to linkage analysis in a large family with multiple hereditary trichoepithelioma (TE) from Algeria. Linkage to 9p21 was excluded, whereas CYLD remained as a candidate. Mutation analysis identified a single bp germ-line deletion expected to result in truncation or absence of the encoded protein, which segregated with the multiple TE phenotype. In individual tumors, loss of heterozygosity at 16q or a somatic point mutation in the CYLD gene was detected. Hence, mutations of the tumor suppressor gene CYLD at 16q12-q13 may give rise to familial TE indistinguishable from the phenotype assigned to 9p21.
Salhi
Aicha
A
Department of Dermatology, University of Algiers, Algiers, Algeria.
Bornholdt
Dorothea
D
Oeffner
Frank
F
Malik
Sajid
S
Heid
Ernest
E
Happle
Rudolf
R
Grzeschik
Karl-Heinz
KH
D000328:Adult; D000462:Algeria; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D000074749:Deubiquitinating Enzyme CYLD; D005260:Female; D016147:Genes, Tumor Suppressor; D008040:Genetic Linkage; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D018895:Microsatellite Repeats; D000072079:Patched Receptors; D010375:Pedigree; D011956:Receptors, Cell Surface; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D008565:Membrane Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD