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 STKII-negative PJS cases


Hearle, Nicholas, Lucassen, Anneke, Wang, Rubin, Lim, Wendy, Ross, Fiona, Wheeler, Robert, Moore, Isabella, Shipley, Janet and Houlston, Richard (2004) 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 STKII-negative PJS cases. Genes Chromosomes & Cancer, 41, (2), 163-169. (doi:10.1002/gcc.20067).

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Original Publication URL: http://dx.doi.org/10.1002/gcc.20067

Description/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.

Item Type: Article
ISSNs: 1045-2257 (print)
Related URLs:
Keywords: dna, campomelic dysplasia, in situ hybridization, lkb1, time, mutation, female, kinase, interphase, report, infant, families,analysis, sry-related gene, cancer, pigmentation
Subjects: R Medicine > RD Surgery
R Medicine
R Medicine > RM Therapeutics. Pharmacology
Divisions: University Structure - Pre August 2011 > School of Medicine > Developmental Origins of Health and Disease
University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
University Structure - Pre August 2011 > School of Medicine
ePrint ID: 59817
Date Deposited: 04 Sep 2008
Last Modified: 27 Mar 2014 18:41
URI: http://eprints.soton.ac.uk/id/eprint/59817

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