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.
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.
Hearle
Nicholas
N
Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom. nick.hearle@icr.ac.uk
Lucassen
Anneke
A
Wang
Rubin
R
Lim
Wendy
W
Ross
Fiona
F
Wheeler
Robert
R
Moore
Isabella
I
Shipley
Janet
J
Houlston
Richard
R
D000091162:AMP-Activated Protein Kinase Kinases; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D010580:Peutz-Jeghers Syndrome / Q000201:enzymology / Q000235:genetics*; D011127:Polyps / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases