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Evaluation of CFTR gene mutations in Adana

Year 2013, Volume: 38 Issue: 2, 202 - 208, 01.06.2013

Abstract

ABSTRACT Objective: Cystic fibrosis is the most common autosomal recessive inherited disorder seen in the white populations. It develops in result of mutations of cystic fibrosis transmembrane regulator (CFTR) gene. Rate of these mutations vary in different geographical regions. In this study, we aimed to determine the frequency of CFTR gene mutations in Adana. Methods: DNA samples of 63 subjects (21 women, 42 men) who were diagnosed as cystic fibrosis at Balcalı Hospital of Çukurova University, were studied for 19 different CFTR mutations by the strip assay method which is based on reverse hybridization. Results: In cystic fibrosis diagnosed patients, 19 mutations were observed of which 9 were homozygous and 10 were heterozygous. ∆F508 frequency was found as 11.9%, and rate of homozygous was found as 66.7%. Mutation frequencies of W1282X and N1303K were found as 2.40% and 4.80% respectively and rate of homozygous mutations were 50% for both. I148T mutation frequency was found as 3.20% and all were heterozygous. For the whole 19 mutations, frequency of mutation in 63 subjects was 22.3%. Conclusion: Detection of CFTR gene mutations by the strip assay method by reverse hybridization is an easy, fast and informative method. However, due to improvability of the common mutations in probable cystic fibrosis patients because of heterogenity in this region, it is still a major problem and does not exclude cystic fibrosis diagnosis. But this problematic issue can be overcome by evaluating the whole exons of CFTR mutations by advanced molecular tecniques. Key words: CFTR, cystic fibrosis, molecular diagnosis, reverse hibridisationKey words:

References

  • Fraser RG, Peter Pare JA, Pare PD, Fraser RS, Genereux GP. In Bralow L. Diseases of the airways. Diagnosis of Diseases of the Chest. 3rd Ed. Philadelphia: W.B. Saunders Company. 1990; 1208
  • Neyzi O, Ertuğrul T. Pediatri. 2.Baskı. İstanbul: Nobel Tıp Kitabevi. 1990; 867-71.
  • Scotet V, Barton DE, Watson JB, Audrezet MP, McDevitt T, et al. Comparison of the CFTR mutation spectrum in three cohorts of patients of Celtic origin from Britany (France) and Ireland. Hum Mutat. 2003;22:105.
  • Devaney J, Glennon M, Farrell G, et al. Cystic fibrosis mutation frequencies in an Irish population. Clin Genet. 2003;63:121-5.
  • Uzun S. Konjenital Bilateral Vas Deferens Aplazi (CBAVD)’li hastalarda Kistik Fibroz (CF) Genindeki Nokta Mutasyonlarının Araştırılması: CBAVD, CF İlişkisi. (Doktora tezi). İstanbul Üniversitesi Sağlık Bilimleri Enstitüsü Biyofizik Anabilim Dalı, İstanbul. 2000.
  • Radpour R, Gourabi H, Vosough Dizaj A, Holzgreve W, Zhong XY. Genetic Investigations of CFTR Mutations in Congenital Absence of Vas Deferens, Uterus and Vagina as a Cause of Infertility. J Androl. 2008; 29: 506-13.
  • Kiper N, Yalçın E. Kistik Fibrozis. TTB Sürekli Tıp Eğitim Dergisi. 2003; 12: 131-3.
  • Dean M, Will K, Stuhrmann M, Schmidtke J. Alternative Splicing in the First Nucleotide Binding Fold of CFTR. Hum Mol Gen. 1993;2:231-5.
  • Lyon A, Bilton D. Fertility issues in cystic fibrosis. Pediatr Respir Rev. 2002;3:236-40.
  • Mitchell I, Nakielna E, Tullis E, Adair C. Cystic Fibrosis: End-stage care in Canada. Chest. 2000;118:80-4.
  • Hargreave T. Genetic basis of male infertility. B Med Bul. 2000;3:650-71.
  • Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989;245:1059-65.
  • Mueller RF, Young ID. Emery’s Elements of Medical Genetics. Singapore: Longman. 1997;233-43.
  • Brock DJH. Molecular Genetics for Clinician. Cambridge University Press. 1993;168-206.
  • Kerem B, Chiba-Falek O, Kerem E. Cystic fibrosis in Jews: frequency and mutation distribution. Genet Test. 1997;1:35-9.
  • Cuppens H, Cassiman JJ. CFTR mutations and polymorphisms in male infertility. Int J And 2004;27:251-6.
  • Riordan JR. The Cystic Fibrosis Transmembrane Conductance Regulator. Annual Rev. Physiol.1993;55:609-30.
  • Cyctic fibrosis Mutation Database at HYPERLINK http://www.genet.sickkids.on.ca/cftr/ . erişim tarihi: 002012
  • Mennicke K, Klingenberg RD, Bals-Pratsch M, Diedrich K, Schwinger E. Rational approach to genetic testing of cystic fibrosis (CF) in infertile men. Andrologia. 2005;37:1-9.
  • Popli K, Stewart J. Infertility and its management in men with cystic fibrosis: review of literature and clinical practices in the UK. Hum Fertil. 2007;10:217
  • Lissens W, Liebaers I. The genetics of male infertility in relation to cystic fibrosis. Baillieres Clin Obstet Gynaecol. 1997;11:797-817.
  • Schulz S, Jakubiczka S, Kropf S, Nickel I, Muschke P, Kleinstein J. Increased frequency of cystic fibrosis transmembrane conductance regulator gene mutations in infertile males. Fertil Steril. 2006; 85: 135Taylor GR. Polymerase Chain Reaction: Basic
  • Principle and Automation. In: Mc Pherson M.J, Qurkie P, Taylor G.R. PCR Volume 1:A practical approach, 1 st Ed. New York: Oxford University Press.1991;1-14.
  • National Center for Biotechnology Information (NCBI); On line Mendelian Inheritance in Man (OMIM); HYPERLINK http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim219700. Erişim tarihi :07.08.2012
  • Costes B, Girodon E, Ghanem N, Flori E, Jardin A, Soufir JC et al. Frequent occurrence of the CFTR intron 8 (TG)n 5T allele in men with congenital bilateral absence of the vas deferens. EurJ Hum Genet.1995;3:285-93.
  • Schwarz M, Malone G. Methods for Screening in Cystic Fibrosis. In: Elles R (editor). Molecular Diagnosis of Genetic Diseases. New Jersey: Humana Press. 1996;99-119.
  • Wu J, Griffith BB, Bassinger S, Moehlenkamp C, Brodie SG, Y. Wu, et al. Strategies for unambiguous detection of allelic heterozygosity via direct DNA sequencing of PCR pruducts: application to the HLA DRB1 locus. Mol Diagn. 1996;1:89-98.
  • Cystic Fibrosis Genetic Analysis Consortium. Worldwide survey of the ΔF508 mutation report of the Cystic Fibrosis Genetic Analysis Consortium. Am J Hum Genet. 1990;47:354–59.
  • The European Working Group on Cystic Fibrosis Genetics: Origin and diffusion of the major CF mutations in Europe. In Tsui LC (editor): The Identification of the CF Gene. 1 st Ed. New York: Plenum Press. 1991; 63-74.
  • Bobadilla JL, Macek M Jr, Fine JP, Farrell PM. Cystic Fibrosis: A Worldwide Analysis of CFTR Mutations. Correlation With Incidence Data and Application to Screening. Human Mutation. 2002;19:575-606.
  • Cystic Fibrosis Mutation Database. Cystic Fibrosis Centre at the Hospital for Sick Children in Toronto. [Updated on Apr 2010]. http://www.genet.sickkids.on.ca/cftr/Home.html erişim tarihi 08.08.2012
  • Ülgenalp A. Strip Assay Metodu Kullanılarak “Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)”Geni Mutasyonlarının Analizi. Deü tıp fakültesi dergisi. 2009;23:47–51.
  • Shah U, Frossard P, Moatter T. Cystic fibrosis: defining a disease under-diagnosed in Pakistan. Trop Med Int Health. 2009;14:542-5.
  • Messaoud T, Verlingue C, Denamur E, Pascaud O, Quéré I, Fattoum S, et al. Distribution of CFTR mutations in cystic fibrosis patients of Tunisian origin: identification of two novel mutations. Eur J Hum Genet. 1996;4:20-4.
  • Balassopoulou A, Loukopoulos D, Kollia P, Devoto M, Adam G, Arvanitakis S, et al. Cystic firrosis in Greece; typing with DNA probes and identification of the common molecular defect. Hum Genet. 1990;85:393-4.
  • Kalaydjieva L, Antov J, Bronzova J, Vladimirova V, Horst J. Molecular data on cystic fibrosis in Bulgaria. Hum Genet. 1990;85:412-3.
  • Hundrieser J, Bremer S, Peinemann F, Stuhrmann M, Hoffknecht N, Wulf B, et al. Frequency of the ∆F508 deletion in the CFTR gene in Turkish cystic fibrosis patients. Hum Genet. 1990;85:409-11.
  • Yilmaz E, Erdem H, Ozgüç M, Coşkun T, Ozçelik U, Göçmen A, et al. Study of 12 mutations in Turkish cystic fibrosis patients. Hum Hered. 1995;45:175-77.
  • Onay T, Topaloglu O, Zielenski J, Gokgoz N, Kayserili H, Camcioglu Y, et al. Analysis of the CFTR gene in Turkish cystic fibrosis patients: identification of three novel mutations (3172delAC, P1013L and M1028I). Hum Genet. 1998;102:224-30.
  • Köprübasi FF, Malik N, Bösch-al-Jadooa N, Alkan M, Tanac R, Bühler E. Molecular genetic analysis of Turkish cystic fibrosis patients. Ann Genet. 1993;36:1449.
  • Ülgenalp A, Uzuner N, Giray Ö, Bora E, Erçal D. Türk Kistik Fibrozisli Hastalarda 14 Yaygın Mutasyonun Taranması. İzmir Göğüs Hastalıkları ve Hastanesi Eğitim Hastanesi Dergisi. 2000;14:1-4.
  • Onay T, Zielenski J, Topaloglu O, Gokgoz N, Kayserili H, Apak MY et al. Cystic fibrosis mutations as associated haplotypes in Turkish cystic fibrosis patients. Hum Biology. 2001;73:191-203.
  • Estivill X, Bancells C, Ramos C. Geographic distribution and regional origin of 272 cystic fibrosis mutations in European populations. The Biomed CF Mutation Analysis Consortium. Hum Mutat. 1997;10:135-54.
  • Kilinç MO, Ninis VN, Dağli E, Demirkol M, Ozkinay F, Arikan Z. Highest heterogeneity for cystic fibrosis: 36 mutations account for 75% of all CF chromosomes in Turkish patients. Am J Med Genet. 2002; 113:250-7.
  • İnal CT, Yüreğir G, Özer G, Yüksel B. Detection of cystic fibrosis ∆F508 mutation in the Çukurova Region. Turk J Med Sci. 2000;30:605-7.
  • Kerem E, Kalman YM, Yahav Y, Shoshani T, Abeliovich D, Szeinberg A, et al. Highly variable incidence of cystic fibrosis and different mutation distribution among different Jewish ethnic groups in Israel. Hum Genet. 1995;96:193-7.
  • Görüroğlu Öztürk Ö, Karazindiyanoğlu F, Muşlu N, Polat G. Mersin ilinde CFTR gen mutasyonlarının değerlendirilmesi. IX. Ulusal Klinik Biyokimya Kongre Kitabı, 2009;.96-43.
  • Yazışma Adresi / Address for Correspondence: Dr. Özle m Görüroğlu Öztürk Çukurova Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı 01330 Balcalı-ADANA e-mail: ozlem_goruroglu@yahoo.com Tlf: 0 506 264 22 68 Fax: 0 322 338 69 43 geliş tarihi/received :24.09.2012 kabul tarihi/accepted:07.12.2012

Adana İlinde CFTR Gen Mutasyonlarının Değerlendirilmesi

Year 2013, Volume: 38 Issue: 2, 202 - 208, 01.06.2013

Abstract

ÖZET Amaç: Kistik fibrozis (KF) beyaz ırkta en sık gözlenen otozomal resesif özellik gösteren kalıtımsal bir hastalıktır. Bu hastalık kistik fibrozis transmembran regulator (CFTR) genindeki mutasyonlara bağlı olarak gelişir. Mutasyonlardaki dağılım oranları değişik ülke ve bölgelere göre farklılık göstermektedir. Bu çalışmada Adana İlinde CFTR geni mutasyonlarının değerlendirilmesi amaçlanmıştır. Yöntem: Çalışmada KF tanısı alan (21 kadın, 42 erkek) toplam 63 hastanın DNA örnekleri 19 farklı CFTR mutasyonu açısından ters hibridizasyona dayalı "strip assay" yöntemi ile incelenmiştir. Bulgular: KF tanılı hastaların 19"unda (9"unda homozigot, 10"unda heterozigot mutasyon) saptanmıştır. ∆F508 sıklığı %11.90, homozigotluk oranı ise %66.7 olarak bulunmuştur. W1282X mutasyon sıklığı %2.40 ve N1303K mutasyon sıklığı %4.80 bulunmuş olup homozigotluk oranları %50" dir. I148T mutasyonu %3.20 olarak saptanmıştır ve hepsi heterozigottur. Taradağımız 19 mutasyon için hastaların toplam mutasyon oranı ise % 22.3 olarak bulunmuştur. Sonuç: CFTR geni mutasyonlarının rutin laboratuarlarda saptanabilmesi için ters hibridizasyona dayalı "strip assay" tekniği hızlı, kolay ve bilgi verici bir yöntemdir. Bununla birlikte sonuçlarımızdaki heterojenite, şüpheli bir KF vakasında, yaygın bulunan mutasyonların kanıtlanamaması durumu, halen potansiyel bir sorun olarak kalmaya devam etmektedir ve bu durum tanıyı dışlamamaktadır. Bu sorun CFTR mutasyonunun bulunduğu ekzonların tamamının daha ileri moleküler teknikler ile incelenmesiyle ortadan kaldırılabilir.

References

  • Fraser RG, Peter Pare JA, Pare PD, Fraser RS, Genereux GP. In Bralow L. Diseases of the airways. Diagnosis of Diseases of the Chest. 3rd Ed. Philadelphia: W.B. Saunders Company. 1990; 1208
  • Neyzi O, Ertuğrul T. Pediatri. 2.Baskı. İstanbul: Nobel Tıp Kitabevi. 1990; 867-71.
  • Scotet V, Barton DE, Watson JB, Audrezet MP, McDevitt T, et al. Comparison of the CFTR mutation spectrum in three cohorts of patients of Celtic origin from Britany (France) and Ireland. Hum Mutat. 2003;22:105.
  • Devaney J, Glennon M, Farrell G, et al. Cystic fibrosis mutation frequencies in an Irish population. Clin Genet. 2003;63:121-5.
  • Uzun S. Konjenital Bilateral Vas Deferens Aplazi (CBAVD)’li hastalarda Kistik Fibroz (CF) Genindeki Nokta Mutasyonlarının Araştırılması: CBAVD, CF İlişkisi. (Doktora tezi). İstanbul Üniversitesi Sağlık Bilimleri Enstitüsü Biyofizik Anabilim Dalı, İstanbul. 2000.
  • Radpour R, Gourabi H, Vosough Dizaj A, Holzgreve W, Zhong XY. Genetic Investigations of CFTR Mutations in Congenital Absence of Vas Deferens, Uterus and Vagina as a Cause of Infertility. J Androl. 2008; 29: 506-13.
  • Kiper N, Yalçın E. Kistik Fibrozis. TTB Sürekli Tıp Eğitim Dergisi. 2003; 12: 131-3.
  • Dean M, Will K, Stuhrmann M, Schmidtke J. Alternative Splicing in the First Nucleotide Binding Fold of CFTR. Hum Mol Gen. 1993;2:231-5.
  • Lyon A, Bilton D. Fertility issues in cystic fibrosis. Pediatr Respir Rev. 2002;3:236-40.
  • Mitchell I, Nakielna E, Tullis E, Adair C. Cystic Fibrosis: End-stage care in Canada. Chest. 2000;118:80-4.
  • Hargreave T. Genetic basis of male infertility. B Med Bul. 2000;3:650-71.
  • Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989;245:1059-65.
  • Mueller RF, Young ID. Emery’s Elements of Medical Genetics. Singapore: Longman. 1997;233-43.
  • Brock DJH. Molecular Genetics for Clinician. Cambridge University Press. 1993;168-206.
  • Kerem B, Chiba-Falek O, Kerem E. Cystic fibrosis in Jews: frequency and mutation distribution. Genet Test. 1997;1:35-9.
  • Cuppens H, Cassiman JJ. CFTR mutations and polymorphisms in male infertility. Int J And 2004;27:251-6.
  • Riordan JR. The Cystic Fibrosis Transmembrane Conductance Regulator. Annual Rev. Physiol.1993;55:609-30.
  • Cyctic fibrosis Mutation Database at HYPERLINK http://www.genet.sickkids.on.ca/cftr/ . erişim tarihi: 002012
  • Mennicke K, Klingenberg RD, Bals-Pratsch M, Diedrich K, Schwinger E. Rational approach to genetic testing of cystic fibrosis (CF) in infertile men. Andrologia. 2005;37:1-9.
  • Popli K, Stewart J. Infertility and its management in men with cystic fibrosis: review of literature and clinical practices in the UK. Hum Fertil. 2007;10:217
  • Lissens W, Liebaers I. The genetics of male infertility in relation to cystic fibrosis. Baillieres Clin Obstet Gynaecol. 1997;11:797-817.
  • Schulz S, Jakubiczka S, Kropf S, Nickel I, Muschke P, Kleinstein J. Increased frequency of cystic fibrosis transmembrane conductance regulator gene mutations in infertile males. Fertil Steril. 2006; 85: 135Taylor GR. Polymerase Chain Reaction: Basic
  • Principle and Automation. In: Mc Pherson M.J, Qurkie P, Taylor G.R. PCR Volume 1:A practical approach, 1 st Ed. New York: Oxford University Press.1991;1-14.
  • National Center for Biotechnology Information (NCBI); On line Mendelian Inheritance in Man (OMIM); HYPERLINK http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim219700. Erişim tarihi :07.08.2012
  • Costes B, Girodon E, Ghanem N, Flori E, Jardin A, Soufir JC et al. Frequent occurrence of the CFTR intron 8 (TG)n 5T allele in men with congenital bilateral absence of the vas deferens. EurJ Hum Genet.1995;3:285-93.
  • Schwarz M, Malone G. Methods for Screening in Cystic Fibrosis. In: Elles R (editor). Molecular Diagnosis of Genetic Diseases. New Jersey: Humana Press. 1996;99-119.
  • Wu J, Griffith BB, Bassinger S, Moehlenkamp C, Brodie SG, Y. Wu, et al. Strategies for unambiguous detection of allelic heterozygosity via direct DNA sequencing of PCR pruducts: application to the HLA DRB1 locus. Mol Diagn. 1996;1:89-98.
  • Cystic Fibrosis Genetic Analysis Consortium. Worldwide survey of the ΔF508 mutation report of the Cystic Fibrosis Genetic Analysis Consortium. Am J Hum Genet. 1990;47:354–59.
  • The European Working Group on Cystic Fibrosis Genetics: Origin and diffusion of the major CF mutations in Europe. In Tsui LC (editor): The Identification of the CF Gene. 1 st Ed. New York: Plenum Press. 1991; 63-74.
  • Bobadilla JL, Macek M Jr, Fine JP, Farrell PM. Cystic Fibrosis: A Worldwide Analysis of CFTR Mutations. Correlation With Incidence Data and Application to Screening. Human Mutation. 2002;19:575-606.
  • Cystic Fibrosis Mutation Database. Cystic Fibrosis Centre at the Hospital for Sick Children in Toronto. [Updated on Apr 2010]. http://www.genet.sickkids.on.ca/cftr/Home.html erişim tarihi 08.08.2012
  • Ülgenalp A. Strip Assay Metodu Kullanılarak “Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)”Geni Mutasyonlarının Analizi. Deü tıp fakültesi dergisi. 2009;23:47–51.
  • Shah U, Frossard P, Moatter T. Cystic fibrosis: defining a disease under-diagnosed in Pakistan. Trop Med Int Health. 2009;14:542-5.
  • Messaoud T, Verlingue C, Denamur E, Pascaud O, Quéré I, Fattoum S, et al. Distribution of CFTR mutations in cystic fibrosis patients of Tunisian origin: identification of two novel mutations. Eur J Hum Genet. 1996;4:20-4.
  • Balassopoulou A, Loukopoulos D, Kollia P, Devoto M, Adam G, Arvanitakis S, et al. Cystic firrosis in Greece; typing with DNA probes and identification of the common molecular defect. Hum Genet. 1990;85:393-4.
  • Kalaydjieva L, Antov J, Bronzova J, Vladimirova V, Horst J. Molecular data on cystic fibrosis in Bulgaria. Hum Genet. 1990;85:412-3.
  • Hundrieser J, Bremer S, Peinemann F, Stuhrmann M, Hoffknecht N, Wulf B, et al. Frequency of the ∆F508 deletion in the CFTR gene in Turkish cystic fibrosis patients. Hum Genet. 1990;85:409-11.
  • Yilmaz E, Erdem H, Ozgüç M, Coşkun T, Ozçelik U, Göçmen A, et al. Study of 12 mutations in Turkish cystic fibrosis patients. Hum Hered. 1995;45:175-77.
  • Onay T, Topaloglu O, Zielenski J, Gokgoz N, Kayserili H, Camcioglu Y, et al. Analysis of the CFTR gene in Turkish cystic fibrosis patients: identification of three novel mutations (3172delAC, P1013L and M1028I). Hum Genet. 1998;102:224-30.
  • Köprübasi FF, Malik N, Bösch-al-Jadooa N, Alkan M, Tanac R, Bühler E. Molecular genetic analysis of Turkish cystic fibrosis patients. Ann Genet. 1993;36:1449.
  • Ülgenalp A, Uzuner N, Giray Ö, Bora E, Erçal D. Türk Kistik Fibrozisli Hastalarda 14 Yaygın Mutasyonun Taranması. İzmir Göğüs Hastalıkları ve Hastanesi Eğitim Hastanesi Dergisi. 2000;14:1-4.
  • Onay T, Zielenski J, Topaloglu O, Gokgoz N, Kayserili H, Apak MY et al. Cystic fibrosis mutations as associated haplotypes in Turkish cystic fibrosis patients. Hum Biology. 2001;73:191-203.
  • Estivill X, Bancells C, Ramos C. Geographic distribution and regional origin of 272 cystic fibrosis mutations in European populations. The Biomed CF Mutation Analysis Consortium. Hum Mutat. 1997;10:135-54.
  • Kilinç MO, Ninis VN, Dağli E, Demirkol M, Ozkinay F, Arikan Z. Highest heterogeneity for cystic fibrosis: 36 mutations account for 75% of all CF chromosomes in Turkish patients. Am J Med Genet. 2002; 113:250-7.
  • İnal CT, Yüreğir G, Özer G, Yüksel B. Detection of cystic fibrosis ∆F508 mutation in the Çukurova Region. Turk J Med Sci. 2000;30:605-7.
  • Kerem E, Kalman YM, Yahav Y, Shoshani T, Abeliovich D, Szeinberg A, et al. Highly variable incidence of cystic fibrosis and different mutation distribution among different Jewish ethnic groups in Israel. Hum Genet. 1995;96:193-7.
  • Görüroğlu Öztürk Ö, Karazindiyanoğlu F, Muşlu N, Polat G. Mersin ilinde CFTR gen mutasyonlarının değerlendirilmesi. IX. Ulusal Klinik Biyokimya Kongre Kitabı, 2009;.96-43.
  • Yazışma Adresi / Address for Correspondence: Dr. Özle m Görüroğlu Öztürk Çukurova Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı 01330 Balcalı-ADANA e-mail: ozlem_goruroglu@yahoo.com Tlf: 0 506 264 22 68 Fax: 0 322 338 69 43 geliş tarihi/received :24.09.2012 kabul tarihi/accepted:07.12.2012
There are 48 citations in total.

Details

Primary Language Turkish
Journal Section Research
Authors

Özlem Görüroğlu Öztürk This is me

Filiz Kibar This is me

Esin Damla Ziyanoğlu Karaçor This is me

Salih Çetiner This is me

Gülhan Şahin This is me

Akgün Yaman This is me

Publication Date June 1, 2013
Published in Issue Year 2013 Volume: 38 Issue: 2

Cite

MLA Öztürk, Özlem Görüroğlu et al. “Adana İlinde CFTR Gen Mutasyonlarının Değerlendirilmesi”. Cukurova Medical Journal, vol. 38, no. 2, 2013, pp. 202-8.