Abstract
Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Catalytic Domain
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Chromosomes, Human, Pair 16 / genetics
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Cloning, Molecular
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Contig Mapping
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Deubiquitinating Enzyme CYLD
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Exons / genetics
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Female
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Genes, Dominant / genetics
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Genes, Tumor Suppressor / genetics*
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Genetic Predisposition to Disease / genetics*
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Germ-Line Mutation / genetics
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Humans
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Loss of Heterozygosity / genetics
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Male
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Molecular Sequence Data
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Mutation / genetics
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Neoplasms, Multiple Primary / genetics*
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Neoplasms, Multiple Primary / pathology
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Polymorphism, Genetic / genetics
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Proteins / chemistry
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Proteins / genetics*
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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Sequence Homology, Amino Acid
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Sequence Tagged Sites
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Skin Neoplasms / genetics*
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Skin Neoplasms / pathology
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Thiolester Hydrolases / chemistry
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Tumor Suppressor Proteins*
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Ubiquitin Thiolesterase
Substances
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Proteins
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RNA, Messenger
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Tumor Suppressor Proteins
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Thiolester Hydrolases
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CYLD protein, human
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Deubiquitinating Enzyme CYLD
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Ubiquitin Thiolesterase