Novel mutations in the PATCHED gene in basal cell nevus syndrome.
Basal cell nevus syndrome (BCNS) is an autosomal dominant disease characterized by the presence of multiple basal cell carcinomas, odontogenic keratocysts, palmoplantar pits, and calcification in the falx cerebri caused by mutational inactivation of the PTCH gene. To investigate the molecular basis of BCNS in Chinese, we did a mutational analysis of the PTCH gene by performing denaturing high-performance liquid chromatography in three BCNS families. In this study, three novel mutations, two 1-bp frameshift insertions, i.e., 1468insA and 2392insC, and one 8-bp deletion, i.e., IVS5 + 1delGTAAGTGT, affecting a donor splice site, were identified. All the mutations cause a shift of the open reading frames and lead to premature termination of PTCH protein translation. Our results showed that mutational inactivation of the PTCH gene causes BCNS in Chinese.
Lam
Ching-Wan
CW
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA. ching-wanlam@cuhk.edu.hk
Leung
Chi-Yan
CY
Lee
Kam-Cheong
KC
Xie
Jingwu
J
Lo
Fai-Man
FM
Au
Tak-Shing
TS
Tong
Sui-Fan
SF
Poon
Miu-Kuen
MK
Chan
Loi-Yuen
LY
Luk
Nai-Ming
NM
D000328:Adult; D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D002648:Child; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface; D017384:Sequence Deletion
D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface