Patched homologue 1 mutations in four Japanese families with basal cell nevus syndrome.
OBJECTIVE
To search for patched homologue 1 (PTCH1) mutations in four families with basal cell nevus syndrome (BCNS).


METHODS
Mutation analysis of PTCH1 in unrelated Japanese families affected with BCNS was carried out by direct sequencing.


RESULTS
Six novel PTCH1 mutations, 833G-->A in exon 6, 1415C-->A and 1451G-->T in exon 10, 2798delC in exon 17, 2918-2925dupAGTTCCCT in exon 18 and 3956C-->A in exon 23, were identified.


CONCLUSIONS
Among the six PTCH1 mutations, two frameshift mutations (2798delC and 2918-2925dupAGTTCCCT) and one nonsense mutation (833G-->A) are predicted to lead to premature termination of PTCH1 protein translation. Three simultaneous mutations, 1415C-->A (A472D) and 1451G-->T (G484V) in exon 10, and 3956G-->A (R1319H) in exon 23, were found on one allele in only affected members in one family and none of them were found among 90 unrelated healthy Japanese. The three mutations on one chromosome may have resulted from errors in the recombinational repair process and this is the first report on the PTCH1 mutations due to such a mechanism.
Matsuzawa
N
N
Department of Oral and Maxillofacial Surgery II, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
Nagao
T
T
Shimozato
K
K
Niikawa
N
N
Yoshiura
K-I
KI
D000293:Adolescent; D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000235:genetics*
D018389:Codon, Nonsense; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface