Mapping of a translocation breakpoint in a Peutz–Jeghers hamartoma to the putative PJS locus at 19q13.4 and mutation analysis of candidate genes in polyp and STK11‐negative PJS cases

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Abstract
Germ‐line mutations in the serine‐threonine kinase gene STK11 (LKB1) cause Peutz–Jeghers syndrome (PJS), a rare autosomal dominantly inherited disease, characterized by hamartomatous polyposis and mucocutaneous pigmentation. STK11 mutations only account for about half of PJS cases, and a second disease locus has been proposed at chromosome segment 19q13.4 on the basis of genetic linkage analysis in one family. We identified a t(11;19)(q13;q13.4) in a PJS polyp arising from the small bowel in a female infant age 6 days. Because the breakpoint in 19q13.4 may disrupt the putative PJS disease gene mapping to this region, we mapped the breakpoint and analyzed DNA from the case and a series of STK11‐negative PJS cases. Using two‐color interphase fluorescence in situ hybridization, the breakpoint region was refined to a 0.5‐Mb region within 19q13.4. Eight candidate genes mapping to the breakpoint region—U2AF2, EPN1, NALP4, NALP11, NALP5, ZNF444, PTPRH, and KIAA1811—were screened for mutations in germ‐line and polyp DNA from the case and from 15 PJS cases that did not harbor germ‐line STK11 mutations. No pathogenic mutations in the candidate genes were identified. This report provides further evidence of the existence of a second PJS disease locus at 19q13.4 and excludes involvement of eight candidate genes.