Molecular analysis of CFTR gene mutations among Iraqi cystic fibrosis patients
Tóm tắt
Cystic fibrosis (CF) is an autosomal recessive multisystem disease that results from mutation(s) of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. More than 2100 mutations and polymorphisms have been reported in this gene so far. Incidence and genotyping of CF are under-identified in Iraq. This study aims to determine the types and frequencies of certain CFTR mutations among a sample of Iraqi CF patients. Two groups of patients were included: 31 clinically confirmed CF patients in addition to 47 clinically suspected patients of CF. All confirmed patients had typical, moderate-severe clinical presentation and course of the disease. Molecular analysis was performed on the majority of enrolled patients using the CF-stripAssay® kit supplied by ViennaLab diagnostics, GmbH, Austria. The mutation-detection rate from the tested 34 mutations in this study was 19.5% and the 8 detected mutations were as follows: 3120+1G>A and W1282X were found in 3 (4.17%) patients each; F508del and R1162X were found in 2 (2.78%) patients each; 3272-26A>G, R347P, I507del, and 2183AA>G were found in 1 (1.38%) patient each. Polymorphic variants of IVS8, namely 5T, 7T, and 9T, were detected in ~ 70%. These results were nearly similar to what was reported in regional countries. Cystic fibrosis seems to be not rare as previously thought. 3120+1G>A and W1282X are the two most commonly detected mutations. F508del needs to be included in all future tests, while the I507del mutation was uniquely reported in this study but not in regional studies.
Tài liệu tham khảo
Egan ME, Green DM, Voynow JA (2019) Cystic fibrosis. In: Kligman RM, Stanton BF, ST Geme JW III, Schor NF (eds) Nelson Textbook of Pediatrics, vol 2. Elsevier Inc, pp 2098–2113
Kambouris M, Banjar H, Moggari I, Nazer H, Al-Hamed M, Meyer BF (2000) Identification of novel mutations in Arabs with cystic fibrosis and their impact on the cystic fibrosis transmembrane regulator mutation detection rate in Arab populations. Eur J Pediatr 159(5):303–309
Al-Ghamdi SA (2017) Cystic fibrosis and consanguinity in the Saudi Arabian population. Nat Sci 15(5):6–10
Cystic fibrosis mutation database. 2021. http://www.genet.sickkids.on.ca/StatisticsPage.html. Accessed 2 Mar 2021.
De Boeck K, Zolin A, Cuppens H, Olesen HV, Viviani L (2014) The relative frequency of CFTR mutation classes in European patients with cystic fibrosis. J Cyst Fibros 13(4):403–409
Banjar H (1999) Overview of cystic fibrosis: patients aged 1-12 years in a tertiary care center in Saudi Arabia. Middle East Pediatr 4(2):44–49
Dequeker E, Stuhrmann M, Morris MA, Casals T, Castellani C, Claustres M et al (2009) Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders--updated European recommendations. Eur J Hum Genet 17(1):51–65
Zaidan A, Salman J, Arif H (2020) The spectrum of mutations analysis of exons 10 and 17a of CFTR gene in Iraqi patients with cystic fibrosis disease. Biochem Cell Arch 20(2):6177–6181
Al-Sadeq D, Abunada T, Dalloul R, Fahad S, Taleb S, Aljassim K et al (2019) Spectrum of mutations of cystic fibrosis in the 22 Arab countries: A systematic review. Respirology. 24(2):127–136
Hamamy H (2012 Jul) Consanguineous marriages: preconception consultation in primary health care settings. J Commun Genet 3(3):185–192
Al-Rahal NK (2018 Oct 1) Inherited bleeding disorders in iraq and consanguineous marriage. Int J Hematol Oncol Stem Cell Res 12(4):273–281
Shahin WA, Mehaney DA, El-Falaki MM (2016) Mutation spectrum of Egyptian children with cystic fibrosis. Springerplus. 5(1):686
Reisi M, Behnam M, Sayedi S, Salimi F, Kargar P, Salehi M et al (2019) Prevalence of cystic fibrosis trans-membrane conductance regulator gene common mutations in children with cystic fibrosis in Isfahan, Iran. Int J Pediatr 7(4):9333–9339
El-Falaki MM, Shahin WA, El-Basha NR, Ali AA, Mehaney DA, El-Attar MM (2014 Sep) Profile of cystic fibrosis in a single referral center in Egypt. J Adv Res 5(5):563–568
Macek M Jr, Mackova A, Hamosh A, Hilman BC, Selden RF, Lucotte G et al (1997) Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%. Am J Hum Genet 60(5):1122–1127
Alibakhshi R, Kianishirazi R, Cassiman JJ, Zamani M, Cuppens H (2008 Mar) Analysis of the CFTR gene in Iranian cystic fibrosis patients: identification of eight novel mutations. J Cyst Fibros 7(2):102–109
Laufer-Cahana A, Lerer I, Sagi M, Rachmilewitz-Minei T, Zamir C, Rivlin JR et al (1999) Cystic fibrosis mutations in Israeli Arab patients. Hum Mutat 14(6):543
arra C, Menassa R, Awwad J, Morel Y, Salameh P, Yazbeck N, et al. (2010) Mutational spectrum of cystic fibrosis in the Lebanese population. J Cyst Fibros 9(6):406–410
Storm K, Moens E, Vits L, Vlieger HD et al (2007) High incidence of the CFTR mutations 3272-26A→G and L927P in Belgian cystic fibrosis patients, and identification of three new CFTR mutations (186-2A→G, E588V, and 1671insTATCA). J Cyst Fibros 6(6):371–375
Al-Abadi B, Al-Hiary M, Khasawneh R, Al-Momani A, Bani-Salameh A, Al-Saeidat S et al (2019) Cystic fibrosis gene mutation frequency among a group of suspected children in king hussein medical center, REVIEW. Med Arch 73(2):118–120
Estivill X, Bancells C, Ramos C (1997) Geographic distribution and regional origin of 272 cystic fibrosis mutations in European populations. The biomed CF mutation analysis consortium. Hum Mutat 10(2):135–154
Kýlýnc MO, Ninis VN, Dag E, Demirko M, Ozkýnay F, Arýkan Z et al (2002) Highest heterogeneity for cystic fibrosis: 36 mutations account for 75% of all CF chromosomes in Turkish patients. Am J Hum Genet 113:250–257
Castellani C, Gomez Lira M, Frulloni L, Delmarco A, Marzari M, Bonizzato A et al (2001) Analysis of the entire coding region of the cystic fibrosis transmembrane regulator gene in idiopathic pancreatitis. Hum Mutat 18(2):166
Jackson A, Foley L, Daly L, Fitzpatrick P, Harrington M, Zhou S et al (2010) Delayed cystic fibrosis presentation in children in the absence of newborn screening. Ir Med J 103(4):113–116
Gasparini P, Borgo G, Mastella G, Bonizzato A, Dognini M, Pignatti PF (1992) Nine cystic fibrosis patients homozygous for the CFTR nonsense mutation R1162X have mild or moderate lung disease. J Med Genet 29(8):558–562
Jianmin Y, Kevin C, Tao Z, Zhiling L, Ya N, Zhongxiang N (2011) Association of genetic variants in CFTR gene, IVS8 c.1210-12T[5_9] and c.1210-35_1210-12GT[8_12], with spermatogenetic failure: Case-control study and meta-analysis. Mol Hum Reprod 17(9):594–603
Chillon M, Casals T, Mercier B, Bassas L, Lissens W, Silber S, Romey MC, Ruiz-Romero J, Verlingue C, Claustres M et al (1995) Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med 332(22):1475–1480
Grangeia A, Niel F, Carvalho F et al (2004) Characterization of cystic fibrosis conductance transmembrane regulator gene mutations and IVS8 poly(T) variants in Portuguese patients with congenital absence of the vas deferens. Hum Reprod 19:2502–2508
Huang Q, Ding W, Wei MX (2008) Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470Vin a healthy Chinese population. World J Gastroenterol 14:1925–1930
Tabaripoura R, Niakib HA, Doukic MR et al (2012) Poly thymidine polymorphism and cystic fibrosis in a non-Caucasian population. Dis Markers 32:241–246
Desgeorges M, Mégarbané A, Guittard C et al (1997) Cystic fibrosis in Lebanon: distribution of CFTR mutations among Arab communities. Hum Genet 100:279–283
Al-Musawi BMS, Al-Allawi N, Abdul-Majeed BA, Eissa AA, Jubrael JMS, Hamamy H (2012) Molecular characterization of glucose-6-phosphate dehydrogenase deficient variants in Baghdad city - Iraq. BMC Blood Disord 12(1):4