title: Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz-Jeghers syndrome.
abstract: Peutz-Jeghers syndrome (PJS) is a rare hereditary syndrome characterized by the occurrence of hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation and increased risk of cancer in multiple internal organs. PJS is preconditioned by the manifestation of mutations in the STK11 gene. The majority of detected STK11 changes are small scale mutations, however recent studies showed the significant contribution of medium-sized changes commonly known as copy number variations (CNVs). Here we present a novel 7001 bps deletion of STK11 gene fragment, in which we identified the presence of breakpoints (BPs) within the Alu elements. Comparative meta-analysis with the 80 other CNV cases from 12 publications describing STK11 mutations in patients with PJS revealed the participation of specific Alu elements in all deletions of exons 2-3 so far described. Moreover, we have shown their involvement in the two other CNVs, deletion of exon 2 and deletion of exon 1-3 respectively. Deletion of exons 2-3 of the STK11 gene may prove to be the most recurrent large rearrangement causing PJS. In addition, the sequences present in its BPs may be involved in a formation of a significant percentage of the remaining gene CNVs. This gives a new insight into the conditioning of this rare disease and enables improvements in PJS genetic diagnostics.
authors.affiliation: Institute of Human Genetics, Polish Academy of Science, Strzeszynska 32, 60-479, Poznan, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Borun
authors.forename: Marina
authors.initials: M
authors.lastname: De Rosa
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Nedoszytko
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Walkowiak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Plawski
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000328:Adult; D020087:Alu Elements; D003198:Computer Simulation; D056915:DNA Copy Number Variations; D005091:Exons; D005260:Female; D006801:Humans; D009154:Mutation; D010580:Peutz-Jeghers Syndrome / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases
references.citation: Gastroenterology. 2010 Jun;138(7):2558-60
references.pmid: 20435009
references.citation: Nucleic Acids Res. 2002 Jun 15;30(12):e57
references.pmid: 12060695
references.citation: Hum Genet. 2014 May;133(5):535-45
references.pmid: 24233542
references.citation: Genes Dev. 1998 May 1;12(9):1381-9
references.pmid: 9573054
references.citation: Clin Genet. 1999 Aug;56(2):136-41
references.pmid: 10517250
references.citation: Curr Opin Genet Dev. 2004 Dec;14(6):603-8
references.pmid: 15531153
references.citation: J Clin Pathol. 2005 Jan;58(1):15-9
references.pmid: 15623475
references.citation: Acta Dermatovenerol Alp Pannonica Adriat. 2005 Mar;14(1):26-9
references.pmid: 15818443
references.citation: Hum Mutat. 2005 Dec;26(6):513-9
references.pmid: 16287113
references.citation: J Med Genet. 2006 Apr;43(4):e15
references.pmid: 16582077
references.citation: J Med Genet. 2006 May;43(5):e18
references.pmid: 16648371
references.citation: Genome Res. 2006 Aug;16(8):949-61
references.pmid: 16809666
references.citation: Clin Genet. 2006 Nov;70(5):409-14
references.pmid: 17026623
references.citation: J Mol Diagn. 2006 Nov;8(5):528-33
references.pmid: 17065418
references.citation: J Clin Pathol. 2007 Apr;60(4):392-6
references.pmid: 16775120
references.citation: Dig Dis Sci. 2007 Aug;52(8):1924-33
references.pmid: 17404884
references.citation: Clin Genet. 2007 Dec;72(6):568-73
references.pmid: 17924967
references.citation: Arch Gynecol Obstet. 2008 Jul;278(1):75-7
references.pmid: 18193442
references.citation: Nat Rev Genet. 2009 Aug;10(8):551-64
references.pmid: 19597530
references.citation: Methods. 2010 Apr;50(4):262-70
references.pmid: 20060046
references.citation: Hum Genet. 2010 Oct;128(4):373-82
references.pmid: 20623358
references.citation: Dig Dis Sci. 2010 Dec;55(12):3458-65
references.pmid: 20393878
references.citation: BMC Med Genet. 2010;11:169
references.pmid: 21118512
references.citation: Gut. 2012 Feb;61(2):322; author reply 322-3
references.pmid: 21330574
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5880-5
references.pmid: 22451936
references.citation: Int Urol Nephrol. 2012 Aug;44(4):1045-8
references.pmid: 22160729
references.citation: Clin Genet. 2013 Apr;83(4):365-9
references.pmid: 22775437
references.citation: BMC Med Genet. 2013;14:58
references.pmid: 23718779
references.citation: J Soc Biol. 1999;193(1):29-34
references.pmid: 10851553