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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

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
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.
dna, campomelic dysplasia, in situ hybridization, lkb1, time, mutation, female, kinase, interphase, report, infant, families, analysis, sry-related gene, cancer, pigmentation
1045-2257
163-169
Hearle, Nicholas
8daeff8f-b957-41c3-abd4-8e98e368b709
Lucassen, Anneke
2eb85efc-c6e8-4c3f-b963-0290f6c038a5
Wang, Rubin
73b1893f-625b-409e-981e-8d283e227b57
Lim, Wendy
b175cd39-7c83-494c-a1d6-0f6f64d84a6a
Ross, Fiona
ec0958f8-b992-4e4a-b7e3-c474600390ba
Wheeler, Robert
81d94930-d9d7-486f-8db1-b9e57ed04a8d
Moore, Isabella
99ac7ac6-9293-459d-aaf4-85066997b8bd
Shipley, Janet
c4bd3760-d826-42ba-8321-ce78582034ac
Houlston, Richard
57b6a807-7647-4fe4-aaf6-59478033fc17
Hearle, Nicholas
8daeff8f-b957-41c3-abd4-8e98e368b709
Lucassen, Anneke
2eb85efc-c6e8-4c3f-b963-0290f6c038a5
Wang, Rubin
73b1893f-625b-409e-981e-8d283e227b57
Lim, Wendy
b175cd39-7c83-494c-a1d6-0f6f64d84a6a
Ross, Fiona
ec0958f8-b992-4e4a-b7e3-c474600390ba
Wheeler, Robert
81d94930-d9d7-486f-8db1-b9e57ed04a8d
Moore, Isabella
99ac7ac6-9293-459d-aaf4-85066997b8bd
Shipley, Janet
c4bd3760-d826-42ba-8321-ce78582034ac
Houlston, Richard
57b6a807-7647-4fe4-aaf6-59478033fc17

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 STK11-negative PJS cases. Genes, Chromosomes and Cancer, 41 (2), 163-169. (doi:10.1002/gcc.20067).

Record type: Article

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.

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More information

Submitted date: 9 February 2003
Published date: 1 October 2004
Keywords: dna, campomelic dysplasia, in situ hybridization, lkb1, time, mutation, female, kinase, interphase, report, infant, families, analysis, sry-related gene, cancer, pigmentation
Organisations: Cancer Sciences, Dev Origins of Health & Disease, Medicine

Identifiers

Local EPrints ID: 26380
URI: http://eprints.soton.ac.uk/id/eprint/26380
ISSN: 1045-2257
PURE UUID: 0ce866c0-a87b-432d-9d67-0ab9f4ed03e0
ORCID for Anneke Lucassen: ORCID iD orcid.org/0000-0003-3324-4338

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Date deposited: 21 Apr 2006
Last modified: 16 Mar 2024 03:23

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Contributors

Author: Nicholas Hearle
Author: Anneke Lucassen ORCID iD
Author: Rubin Wang
Author: Wendy Lim
Author: Fiona Ross
Author: Robert Wheeler
Author: Isabella Moore
Author: Janet Shipley
Author: Richard Houlston

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