CYLD mutation causes multiple familial trichoepithelioma in three Chinese families.
Multiple familial trichoepithelioma (MFT) and familial cylindromatosis are two clinically distinct cancer syndromes. MFT patients developed mostly trichoepithelioma in the face while cylindromatosis patients developed cylindromas predominantly (approximately 90%) on the head and neck. However, multiple familial trichoepithelioma is occasionally associated with familial cylindromatosis while cylindromatosis patients can also develop trichoepithelioma. This has led to the speculation that the 2 types of dermatoses may be caused by dysfunction of a common pathway. Previously, a candidate MTF locus has been mapped to 9p21 while disease gene for familial cylindromatosis, the CYLD gene located on 16q21-13 has been identified. Here, we show that mutations in the CYLD gene are also the genetic basis for three different Chinese families with MFT. Sequence analysis reveal a single nucleotide deletion, c.1462delA (P.Ile488fsX9) in exon 9, a nonsense mutation, c.2128C>T (p. Gln710X) in exon 17, and a missense mutation, c.2822A>T (p. Asp941Val) in exon 21 in each of the three families respectively. This provides direct evidence that the mutations in CYLD can cause two clinically distinct cancer syndromes.
Zheng
Guangyong
G
Health Science Center, Shanghai Institutes of Biological Science, Chinese Academy of Science and Shanghai Second Medical University, Shanghai, The People's Republic of China.
Hu
Landian
L
Huang
Wei
W
Chen
Kaide
K
Zhang
Xuejun
X
Yang
Sen
S
Sun
Jianfang
J
Jiang
Yiqun
Y
Luo
Guangbin
G
Kong
Xiangyin
X
D002681:China; D002899:Chromosomes, Human, Pair 9; D000074749:Deubiquitinating Enzyme CYLD; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D018295:Neoplasms, Basal Cell / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD