PCR-RFLP analysis as an aid to genetic counseling of families of Japanese patients with group A xeroderma pigmentosum.

Because Japanese patients with complementation group A xeroderma pigmentosum (XP-A) show early skin cancer and severe neurologic dysfunction, their family members are greatly concerned about the risk of inherited disease. In contrast to western XP-A patients, almost all Japanese XP-A patients have two of the three mutations (nonsense mutation in exon 3, splicing mutation in intron 3, and non-sense mutation in exon 6), which are easily detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. This work was aimed to see whether PCR-RFLP analysis is useful for genetic counseling of XP patients' siblings who are potential carriers of an XP-A gene mutation. In two of the three case studies presented, the probands were homozygous for the splicing mutation in intron 3 of the gene. In their siblings receiving genetic counseling, no mutation was found in the mutation site in one case, and one splicing mutation was found in the second case. In the third case, the proband was a compound heterozygote for the splicing mutation and for an unidentified mutation; in her sibling, no mutation was found in either of these mutation sites. No mutation was found in the siblings' spouses. On the basis of these findings, we reassured the prospective parents that there was little probability of having XP children, but in the second and third cases, we told them that their apparently unaffected children might be carriers. Each couple subsequently had one unaffected child. Thus, PCR-RFLP analysis is useful for genetic counseling of family members of XP-A patients.