MAPPING THE MULTIPLE SELF-HEALING SQUAMOUS EPITHELIOMA (MSSE) GENE AND INVESTIGATION OF XERODERMA-PIGMENTOSUM GROUP-A (XPA) AND PATCHED (PTCH) AS CANDIDATE GENES

The MSSE gene predisposes to the development of multiple invasive but self-healing skin rumours (multiple self-healing squamous epitheliomat a, MSSE). MSSE (previously named ESS1) was mapped to chromosome 9q by linkage analysis; haplotype analysis in families then suggested a comm on founder mutation and indicated that the gene lies in the interval D 9S1-D9S29 (9q22-q31), Squamous cell carcinomata also develop as one of the complications of xeroderma pigmentosum, and one of the xeroderma pigmentosum genes (XPA) maps within the MSSE interval. We have investi gated the hypothesis that a novel dominant mutation in XPA is responsi ble for MSSE. We screened the entire coding region, 3' untranslated re gion (UTR) and 5'UTR of XPA for germline mutations in MSSE families by single-stranded conformation polymorphism analysis and by direct DNA sequencing. No mutations were detected but a novel intragenic polymorp hism was identified in the 5'UTR of XPA, in both MSSE-affected and unr elated normal individuals. This XPA polymorphism and nine new polymorp hic markers that map in the MSSE region were typed in eleven MSSE fami lies; XPA was excluded as the MSSE gene and the most likely location o f MSSE was reduced to the interval between D9S197 and (D9S287, D9S1809 ). The Patched (PTCH) gene, which is mutated in naevoid basal cell car cinoma syndrome (NBCCS or Gorlin syndrome) lies in this interval and a ll MSSE families have been shown to share a common haplotype at three novel intragenic PTCH polymorphisms. Although no mutation has been det ected in MSSE families, PTCH has not been excluded as the MSSE gene.