Germline PTCH1 mutations in Japanese basal cell nevus syndrome patients.
Basal cell nevus syndrome (BCNS or Gorlin syndrome, OMIM: 109400) is a rare autosomal dominant disorder with high penetrance. It is characterized by developmental anomalies and predisposition to tumors (for example, basal cell carcinoma (BCC) and medulloblastoma). PTCH1, the human homolog of the Drosophila patched gene, was identified as a gene responsible for BCNS. The PTCH1 protein is a Hedgehog (Hh) protein receptor and is pivotal for early development, stem cell maintenance and/or differentiation. We analyzed the six Japanese families with BCNS and identified six germline mutations in the PTCH1 gene. One family had a nonsense mutation (c.1196G>A), one had a 1-bp deletion (c.2029delA), two had 2-bp deletions (c.239_240delGA and c.1670_1671delCA) and one had a 58-bp duplication (c.1138_1195dup). They caused premature termination, resulting in the truncation of the PTCH1 protein. Analysis of a high-density single nucleotide polymorphism (SNP) mapping array showed a large approximately 1.2-Mb deletion, including the PTCH1 gene in one allele, in a family in which PTCH1 mutations were not identified at the sequence level. These data indicated that all the six families who were diagnosed with BCNS had mutations in the PTCH1 gene and that a single copy of a PTCH1 mutation causes BCNS.
Takahashi
Chiaki
C
Department of Pediatrics, Hyogo College of Medicine, Nishinomiya, Japan.
Kanazawa
Nozomi
N
Yoshikawa
Yoshie
Y
Yoshikawa
Reigetsu
R
Saitoh
Yuko
Y
Chiyo
Hideaki
H
Tanizawa
Takakuni
T
Hashimoto-Tamaoki
Tomoko
T
Nakano
Yoshiro
Y
D000328:Adult; D044466:Asian People / Q000235:genetics; D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*
C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface