TY  - JOUR
AU  - Dork, T
AU  - Macek, M
AU  - Mekus, F
AU  - Tummler, B
AU  - Tzountzouris, J
AU  - Casals, T
AU  - Krebsova, A
AU  - Koudova, M
AU  - Sakmaryova, I
AU  - Macek, M
AU  - Vavrova, V
AU  - Zemkova, D
AU  - Ginter, E
AU  - Petrova, NV
AU  - Ivaschenko, T
AU  - Baranov, V
AU  - Witt, M
AU  - Pogorzelski, A
AU  - Bal, J
AU  - Zekanowsky, C
AU  - Wagner, K
AU  - Stuhrmann, M
AU  - Bauer, I
AU  - Seydewitz, HH
AU  - Neumann, T
AU  - Jakubiczka, S
AU  - Kraus, C
AU  - Thamm, B
AU  - Nechiporenko, M
AU  - Livshits, L
AU  - Mosse, N
AU  - Tsukerman, G
AU  - Kadasi, L
AU  - Ravnik-Glavac, M
AU  - Glavac, D
AU  - Komel, R
AU  - Vouk, K
AU  - Kucinskas, V
AU  - Krumina, A
AU  - Teder, M
AU  - Kocheva, S
AU  - Efremov, GD
AU  - Onay, T
AU  - Kirdar, B
AU  - Malone, G
AU  - Schwarz, M
AU  - Zhou, ZQ
AU  - Friedman, KJ
AU  - Carles, S
AU  - Claustres, M
AU  - Bozon, D
AU  - Verlingue, C
AU  - Ferec, C
AU  - Tzetis, M
AU  - Kanavakis, E
AU  - Cuppens, H
AU  - Bombieri, C
AU  - Pignatti, PF
AU  - Sangiuolo, F
AU  - Jordanova, A
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Sertić, J
AU  - Richter, D
AU  - Rukavina, AS
AU  - Bjorck, E
AU  - Strandvik, B
AU  - Cardoso, H
AU  - Montgomery, M
AU  - Nakielna, B
AU  - Hughes, D
AU  - Estivill, X
AU  - Aznarez, I
AU  - Tullis, E
AU  - Tsui, LC
AU  - Zielenski, J
PY  - 2000
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/138
AB  - 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 Delta F508/CFTRdele2,3(21 kb) with pairwise-matched Delta 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 "A" and the same infrequent intragenic microsatellite haplotype 16-33-13 (IVS8CA-IVS17bTA-IVSI7bCA) 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.
PB  - Springer, New York
T2  - Human Genetics
T1  - 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
EP  - 268
IS  - 3
SP  - 259
VL  - 106
DO  - 10.1007/s004390000246
ER  - 

@article{
author = "Dork, T and Macek, M and Mekus, F and Tummler, B and Tzountzouris, J and Casals, T and Krebsova, A and Koudova, M and Sakmaryova, I and Macek, M and Vavrova, V and Zemkova, D and Ginter, E and Petrova, NV and Ivaschenko, T and Baranov, V and Witt, M and Pogorzelski, A and Bal, J and Zekanowsky, C and Wagner, K and Stuhrmann, M and Bauer, I and Seydewitz, HH and Neumann, T and Jakubiczka, S and Kraus, C and Thamm, B and Nechiporenko, M and Livshits, L and Mosse, N and Tsukerman, G and Kadasi, L and Ravnik-Glavac, M and Glavac, D and Komel, R and Vouk, K and Kucinskas, V and Krumina, A and Teder, M and Kocheva, S and Efremov, GD and Onay, T and Kirdar, B and Malone, G and Schwarz, M and Zhou, ZQ and Friedman, KJ and Carles, S and Claustres, M and Bozon, D and Verlingue, C and Ferec, C and Tzetis, M and Kanavakis, E and Cuppens, H and Bombieri, C and Pignatti, PF and Sangiuolo, F and Jordanova, A and Kušić-Tišma, Jelena and Radojković, Dragica and Sertić, J and Richter, D and Rukavina, AS and Bjorck, E and Strandvik, B and Cardoso, H and Montgomery, M and Nakielna, B and Hughes, D and Estivill, X and Aznarez, I and Tullis, E and Tsui, LC and Zielenski, J",
year = "2000",
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 Delta F508/CFTRdele2,3(21 kb) with pairwise-matched Delta 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 "A" and the same infrequent intragenic microsatellite haplotype 16-33-13 (IVS8CA-IVS17bTA-IVSI7bCA) 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.",
publisher = "Springer, New York",
journal = "Human Genetics",
title = "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",
pages = "268-259",
number = "3",
volume = "106",
doi = "10.1007/s004390000246"
}

Dork, T., Macek, M., Mekus, F., Tummler, B., Tzountzouris, J., Casals, T., Krebsova, A., Koudova, M., Sakmaryova, I., Macek, M., Vavrova, V., Zemkova, D., Ginter, E., Petrova, N., Ivaschenko, T., Baranov, V., Witt, M., Pogorzelski, A., Bal, J., Zekanowsky, C., Wagner, K., Stuhrmann, M., Bauer, I., Seydewitz, H., Neumann, T., Jakubiczka, S., Kraus, C., Thamm, B., Nechiporenko, M., Livshits, L., Mosse, N., Tsukerman, G., Kadasi, L., Ravnik-Glavac, M., Glavac, D., Komel, R., Vouk, K., Kucinskas, V., Krumina, A., Teder, M., Kocheva, S., Efremov, G., Onay, T., Kirdar, B., Malone, G., Schwarz, M., Zhou, Z., Friedman, K., Carles, S., Claustres, M., Bozon, D., Verlingue, C., Ferec, C., Tzetis, M., Kanavakis, E., Cuppens, H., Bombieri, C., Pignatti, P., Sangiuolo, F., Jordanova, A., Kušić-Tišma, J., Radojković, D., Sertić, J., Richter, D., Rukavina, A., Bjorck, E., Strandvik, B., Cardoso, H., Montgomery, M., Nakielna, B., Hughes, D., Estivill, X., Aznarez, I., Tullis, E., Tsui, L.,& Zielenski, J.. (2000). 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. in Human Genetics
Springer, New York., 106(3), 259-268.
https://doi.org/10.1007/s004390000246

Dork T, Macek M, Mekus F, Tummler B, Tzountzouris J, Casals T, Krebsova A, Koudova M, Sakmaryova I, Macek M, Vavrova V, Zemkova D, Ginter E, Petrova N, Ivaschenko T, Baranov V, Witt M, Pogorzelski A, Bal J, Zekanowsky C, Wagner K, Stuhrmann M, Bauer I, Seydewitz H, Neumann T, Jakubiczka S, Kraus C, Thamm B, Nechiporenko M, Livshits L, Mosse N, Tsukerman G, Kadasi L, Ravnik-Glavac M, Glavac D, Komel R, Vouk K, Kucinskas V, Krumina A, Teder M, Kocheva S, Efremov G, Onay T, Kirdar B, Malone G, Schwarz M, Zhou Z, Friedman K, Carles S, Claustres M, Bozon D, Verlingue C, Ferec C, Tzetis M, Kanavakis E, Cuppens H, Bombieri C, Pignatti P, Sangiuolo F, Jordanova A, Kušić-Tišma J, Radojković D, Sertić J, Richter D, Rukavina A, Bjorck E, Strandvik B, Cardoso H, Montgomery M, Nakielna B, Hughes D, Estivill X, Aznarez I, Tullis E, Tsui L, Zielenski J. 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. in Human Genetics. 2000;106(3):259-268.
doi:10.1007/s004390000246 .

Dork, T, Macek, M, Mekus, F, Tummler, B, Tzountzouris, J, Casals, T, Krebsova, A, Koudova, M, Sakmaryova, I, Macek, M, Vavrova, V, Zemkova, D, Ginter, E, Petrova, NV, Ivaschenko, T, Baranov, V, Witt, M, Pogorzelski, A, Bal, J, Zekanowsky, C, Wagner, K, Stuhrmann, M, Bauer, I, Seydewitz, HH, Neumann, T, Jakubiczka, S, Kraus, C, Thamm, B, Nechiporenko, M, Livshits, L, Mosse, N, Tsukerman, G, Kadasi, L, Ravnik-Glavac, M, Glavac, D, Komel, R, Vouk, K, Kucinskas, V, Krumina, A, Teder, M, Kocheva, S, Efremov, GD, Onay, T, Kirdar, B, Malone, G, Schwarz, M, Zhou, ZQ, Friedman, KJ, Carles, S, Claustres, M, Bozon, D, Verlingue, C, Ferec, C, Tzetis, M, Kanavakis, E, Cuppens, H, Bombieri, C, Pignatti, PF, Sangiuolo, F, Jordanova, A, Kušić-Tišma, Jelena, Radojković, Dragica, Sertić, J, Richter, D, Rukavina, AS, Bjorck, E, Strandvik, B, Cardoso, H, Montgomery, M, Nakielna, B, Hughes, D, Estivill, X, Aznarez, I, Tullis, E, Tsui, LC, Zielenski, J, "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" in Human Genetics, 106, no. 3 (2000):259-268,
https://doi.org/10.1007/s004390000246 . .