ORIGINAL ARTICLE

Patched homologue 1 mutations in four Japanese families with basal cell nevus syndrome

N Matsuzawa¹, T Nagao¹, K Shimozato¹, N Niikawa^2,3 and K-i Yoshiura^2,3

¹ Department of Oral and Maxillofacial Surgery II, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
² Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
³ SORST, Japan Science and Technology Agency (JST), Kawaguchi, Japan

Correspondence to:
Correspondence to:
K-i Yoshiura
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki 852-8523, Japan; kyoshi{at}net.nagasaki-u.ac.jp

Aim: 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, 833GA in exon 6, 1415CA and 1451GT in exon 10, 2798delC in exon 17, 2918–2925dupAGTTCCCT in exon 18 and 3956CA in exon 23, were identified.

Conclusions: Among the six PTCH1 mutations, two frameshift mutations (2798delC and 2918–2925dupAGTTCCCT) and one nonsense mutation (833GA) are predicted to lead to premature termination of PTCH1 protein translation. Three simultaneous mutations, 1415CA (A472D) and 1451GT (G484V) in exon 10, and 3956GA (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.

Abbreviations: BCNS, basal cell nevus syndrome; PCR, polymerase chain reaction; PTCH1, patched homologue 1

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