Article: Characterization of a novel 21-kb deletion, CFTRdele2,3(21 kb), in the CFTR gene: A cystic fibrosis mutation of Slavic origin common in Central and East Europe

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TitleCharacterization of a novel 21-kb deletion, CFTRdele2,3(21 kb), in the CFTR gene: A cystic fibrosis mutation of Slavic origin common in Central and East Europe
AuthorsDörk, T8
Macek Jr, M14
Mekus, F8
Tümmler, B8
Tzountzouris, J19
Casals, T17
Krebsová, A14
Koudová, M14
Sakmaryová, I14
Macek Sr, M14
Vávrová, V14
Zemková, D14
Ginter, E5
Petrova, NV5
Ivaschenko, T10
Baranov, V10
Witt, M16
Pogorzelski, A1
Bal, J7
Zékanowsky, C7
Wagner, K
Stuhrmann, M8
Bauer, I
Seydewitz, HH2
Neumann, T18
Jakubiczka, S3
Kraus, C13
Thamm, B15
Nechiporenko, M6
Livshits, L6
Mosse, N11
Tsukerman, G11
Kadási, L12
RavnikGlavač, M9
Glavač, D9
Komel, R4
Vouk, K4
Kučinskas, V
Krumina, A
Teder, M
Kocheva, S
Efremov, GD
Onay, T
Kirdar, B
Malone, G
Schwarz, M
Zhou, Z
Friedman, KJ
Carles, S
Claustres, M
Bozon, D
Verlingue, C
Férec, C
Tzetis, M
Kanavakis, E
Cuppens, H
Bombieri, C
Pignatti, PF
Sangiuolo, F
Jordanova, A
Kusic, J
Radojkovič, D
Sertić, J
Richter, D
Rukavina, AS
Bjorck, E
Strandvik, B
Cardoso, H
Montgomery, M
Nakielna, B
Hughes, D
Estivill, X17
Aznarez, I19
Tullis, E
Tsui, LC19
Zielenski, J19
Issue Date2000
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00439/index.htm
CitationHuman Genetics, 2000, v. 106 n. 3, p. 259-268 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s004390000246
AbstractWe report a large genomic deletion of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, viz., a deletion that is frequently observed in Central and Eastern Europe. The mutation, termed CFTRdele2,3(21 kb), deletes 21,080 bp spanning introns 1-3 of the CFTR gene. Transcript analyses have revealed that this deletion results in the loss of exons 2 and 3 in epithelial CFTR mRNA, thereby producing a premature termination signal within exon 4. In order to develop a simple polymerase chain reaction assay for this allele, we defined the end-points of the deletion at the DNA sequence level. We next screened for this mutation in a representative set of European and European-derived populations. Some 197 CF patients, including seven homozygotes, bearing this mutation have been identified during the course of our study. Clinical evaluation of CFTRdele2,3(21 kb) homozygotes and a comparison of compound heterozygotes for ΔF508/CFTRdele2,3(21 kb) with pairwise-matched ΔF508 homozygotes indicate that this deletion represents a severe mutation associated with pancreatic insufficiency and early age at diagnosis. Current data show that the mutation is particularly common in Czech (6.4% of all CF chromosomes), Russian (5.2%), Belorussian (3.3%), Austrian (2.6%), German (1.5%), Polish (1.5%), Slovenian (1.5%), Ukrainian (1.2%), and Slovak patients (1.1%). It has also been found in Lithuania, Latvia, Macedonia and Greece and has sporadically been observed in Canada, USA, France, Spain, Turkey, and UK, but not in CF patients from Bulgaria, Croatia, Romania or Serbia. Haplotype analysis has identified the same extragenic CF-haplotype XV-2c/KM. 19 'A' and the same infrequent intragenic microsatellite haplotype 16-33-13 (IVS8CA-IVS17bTA-IVS17bCA) in all examined CFTRdele2,3(21 kb) chromosomes, suggesting a common origin for this deletion. We conclude that the 21-kb deletion is a frequent and severe CF mutation in populations of Eastern- and Western-Slavic descent.
ISSN0340-6717
2011 Impact Factor: 5.069
2011 SCImago Journal Rankings: 0.328
DOIhttp://dx.doi.org/10.1007/s004390000246
ISI Accession Number IDWOS:000086661100001
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorDörk, T
dc.contributor.authorMacek Jr, M
dc.contributor.authorMekus, F
dc.contributor.authorTümmler, B
dc.contributor.authorTzountzouris, J
dc.contributor.authorCasals, T
dc.contributor.authorKrebsová, A
dc.contributor.authorKoudová, M
dc.contributor.authorSakmaryová, I
dc.contributor.authorMacek Sr, M
dc.contributor.authorVávrová, V
dc.contributor.authorZemková, D
dc.contributor.authorGinter, E
dc.contributor.authorPetrova, NV
dc.contributor.authorIvaschenko, T
dc.contributor.authorBaranov, V
dc.contributor.authorWitt, M
dc.contributor.authorPogorzelski, A
dc.contributor.authorBal, J
dc.contributor.authorZékanowsky, C
dc.contributor.authorWagner, K
dc.contributor.authorStuhrmann, M
dc.contributor.authorBauer, I
dc.contributor.authorSeydewitz, HH
dc.contributor.authorNeumann, T
dc.contributor.authorJakubiczka, S
dc.contributor.authorKraus, C
dc.contributor.authorThamm, B
dc.contributor.authorNechiporenko, M
dc.contributor.authorLivshits, L
dc.contributor.authorMosse, N
dc.contributor.authorTsukerman, G
dc.contributor.authorKadási, L
dc.contributor.authorRavnikGlavač, M
dc.contributor.authorGlavač, D
dc.contributor.authorKomel, R
dc.contributor.authorVouk, K
dc.contributor.authorKučinskas, V
dc.contributor.authorKrumina, A
dc.contributor.authorTeder, M
dc.contributor.authorKocheva, S
dc.contributor.authorEfremov, GD
dc.contributor.authorOnay, T
dc.contributor.authorKirdar, B
dc.contributor.authorMalone, G
dc.contributor.authorSchwarz, M
dc.contributor.authorZhou, Z
dc.contributor.authorFriedman, KJ
dc.contributor.authorCarles, S
dc.contributor.authorClaustres, M
dc.contributor.authorBozon, D
dc.contributor.authorVerlingue, C
dc.contributor.authorFérec, C
dc.contributor.authorTzetis, M
dc.contributor.authorKanavakis, E
dc.contributor.authorCuppens, H
dc.contributor.authorBombieri, C
dc.contributor.authorPignatti, PF
dc.contributor.authorSangiuolo, F
dc.contributor.authorJordanova, A
dc.contributor.authorKusic, J
dc.contributor.authorRadojkovič, D
dc.contributor.authorSertić, J
dc.contributor.authorRichter, D
dc.contributor.authorRukavina, AS
dc.contributor.authorBjorck, E
dc.contributor.authorStrandvik, B
dc.contributor.authorCardoso, H
dc.contributor.authorMontgomery, M
dc.contributor.authorNakielna, B
dc.contributor.authorHughes, D
dc.contributor.authorEstivill, X
dc.contributor.authorAznarez, I
dc.contributor.authorTullis, E
dc.contributor.authorTsui, LC
dc.contributor.authorZielenski, J
dc.date.accessioned2007-09-12T03:52:06Z
dc.date.available2007-09-12T03:52:06Z
dc.date.issued2000
dc.description.abstractWe report a large genomic deletion of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, viz., a deletion that is frequently observed in Central and Eastern Europe. The mutation, termed CFTRdele2,3(21 kb), deletes 21,080 bp spanning introns 1-3 of the CFTR gene. Transcript analyses have revealed that this deletion results in the loss of exons 2 and 3 in epithelial CFTR mRNA, thereby producing a premature termination signal within exon 4. In order to develop a simple polymerase chain reaction assay for this allele, we defined the end-points of the deletion at the DNA sequence level. We next screened for this mutation in a representative set of European and European-derived populations. Some 197 CF patients, including seven homozygotes, bearing this mutation have been identified during the course of our study. Clinical evaluation of CFTRdele2,3(21 kb) homozygotes and a comparison of compound heterozygotes for ΔF508/CFTRdele2,3(21 kb) with pairwise-matched ΔF508 homozygotes indicate that this deletion represents a severe mutation associated with pancreatic insufficiency and early age at diagnosis. Current data show that the mutation is particularly common in Czech (6.4% of all CF chromosomes), Russian (5.2%), Belorussian (3.3%), Austrian (2.6%), German (1.5%), Polish (1.5%), Slovenian (1.5%), Ukrainian (1.2%), and Slovak patients (1.1%). It has also been found in Lithuania, Latvia, Macedonia and Greece and has sporadically been observed in Canada, USA, France, Spain, Turkey, and UK, but not in CF patients from Bulgaria, Croatia, Romania or Serbia. Haplotype analysis has identified the same extragenic CF-haplotype XV-2c/KM. 19 'A' and the same infrequent intragenic microsatellite haplotype 16-33-13 (IVS8CA-IVS17bTA-IVS17bCA) in all examined CFTRdele2,3(21 kb) chromosomes, suggesting a common origin for this deletion. We conclude that the 21-kb deletion is a frequent and severe CF mutation in populations of Eastern- and Western-Slavic descent.
dc.description.natureabstract
dc.identifier.citationHuman Genetics, 2000, v. 106 n. 3, p. 259-268 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s004390000246
dc.identifier.doihttp://dx.doi.org/10.1007/s004390000246
dc.identifier.epage268
dc.identifier.isiWOS:000086661100001
dc.identifier.issn0340-6717
2011 Impact Factor: 5.069
2011 SCImago Journal Rankings: 0.328
dc.identifier.issue3
dc.identifier.pmid10798353
dc.identifier.scopuseid_2-s2.0-0342657015
dc.identifier.spage259
dc.identifier.urihttp://hdl.handle.net/10722/44361
dc.identifier.volume106
dc.languageeng
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00439/index.htm
dc.publisher.placeGermany
dc.relation.ispartofHuman Genetics
dc.relation.referencesReferences in Scopus
dc.rightsThe original publication is available at www.springerlink.com
dc.subject.meshCystic fibrosis - epidemiology - genetics
dc.subject.meshCystic fibrosis - epidemiology - genetics
dc.subject.meshDna mutational analysis
dc.subject.meshEurope - epidemiology
dc.subject.meshPhenotype
dc.titleCharacterization of a novel 21-kb deletion, CFTRdele2,3(21 kb), in the CFTR gene: A cystic fibrosis mutation of Slavic origin common in Central and East Europe
dc.typeArticle
Author Affiliations
  1. Inst. for TB and Pulmonary Diseases
  2. null
  3. Universität Magdeburg
  4. Univerzitetni Klinični Center Ljubljana
  5. Russian Academy of Sciences
  6. Institute of Molecular Biology and Genetics National Academy of Sciences of Ukraine
  7. Instytut Matki I Dziecka
  8. Medizinische Hochschule Hannover (MHH)
  9. University of Ljubljana Faculty of Medicine, Institute of Pathology
  10. Institute of Obstetrics and Gynecology
  11. Institute of Hereditary Disorders
  12. Comenius University
  13. null
  14. Univerzita Karlova v Praze
  15. Institute of Human Genetics
  16. Polish Academy of Sciences
  17. null
  18. Westfälische Wilhelms-Universität Münster
  19. Hospital for Sick Children, Toronto