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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, T9
Macek Jr, M15
Mekus, F9
Tümmler, B9
Tzountzouris, J17
Casals, T7
Krebsová, A15
Koudová, M15
Sakmaryová, I15
Macek Sr, M15
Vávrová, V15
Zemková, D15
Ginter, E4
Petrova, NV4
Ivaschenko, T11
Baranov, V11
Witt, M
Pogorzelski, A2
Bal, J8
Zékanowsky, C8
Wagner, K
Stuhrmann, M9
Bauer, I
Seydewitz, HH1
Neumann, T18
Jakubiczka, S3
Kraus, C14
Thamm, B16
Nechiporenko, M6
Livshits, L6
Mosse, N12
Tsukerman, G12
Kadási, L13
RavnikGlavač, M10
Glavač, D10
Komel, R5
Vouk, K5
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, X7
Aznarez, I17
Tullis, E
Tsui, LC17
Zielenski, J17
 
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
2012 Impact Factor: 4.633
2012 SCImago Journal Rankings: 1.563
 
DOIhttp://dx.doi.org/10.1007/s004390000246
 
ISI Accession Number IDWOS:000086661100001
 
ReferencesReferences in Scopus
 
DC FieldValue
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
2012 Impact Factor: 4.633
2012 SCImago Journal Rankings: 1.563
 
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
 
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<description.abstract>We 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 &#916;F508/CFTRdele2,3(21 kb) with pairwise-matched &#916;F508 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 &apos;A&apos; 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.</description.abstract>
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Author Affiliations
  1. null
  2. Inst. for TB and Pulmonary Diseases
  3. Universität Magdeburg
  4. Russian Academy of Sciences
  5. Univerzitetni Klinični Center Ljubljana
  6. Institute of Molecular Biology and Genetics National Academy of Sciences of Ukraine
  7. null
  8. Instytut Matki I Dziecka
  9. Medizinische Hochschule Hannover (MHH)
  10. University of Ljubljana Faculty of Medicine, Institute of Pathology
  11. Institute of Obstetrics and Gynecology
  12. Institute of Hereditary Disorders
  13. Comenius University
  14. null
  15. Univerzita Karlova v Praze
  16. Institute of Human Genetics
  17. Hospital for Sick Children University of Toronto
  18. Westfälische Wilhelms-Universität Münster