Molecular Genetics of Cystic Fibrosis Transmembrane Conductance Regulator: Genotype and Phenotype

Pediatric Clinics of North America

Volumn 63, Issue 4, 2016, Pages 585-598

  Sosnay, Patrick R ^a   Raraigh, Karen S ^b   Gibson, Ronald L ^c  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

^c UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

CFTR mutations; Cystic fibrosis; Genotype phenotype correlations

Indexed keywords

CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR;

ALLELE; CFTR GENE; CYSTIC FIBROSIS; EXON; GENE DELETION; GENE DUPLICATION; GENE MUTATION; GENE SEQUENCE; GENETIC SCREENING; HUMAN; MOLECULAR GENETICS; MUTATIONAL ANALYSIS; NEXT GENERATION SEQUENCING; REVIEW; GENETICS; GENOTYPE; MOLECULAR BIOLOGY; MUTATION; PHENOTYPE;

CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; GENOTYPE; HUMANS; MOLECULAR BIOLOGY; MUTATION; PHENOTYPE;

EID: 84997783069     PISSN: 00313955     EISSN: 15578240     Source Type: Journal    
DOI: 10.1016/j.pcl.2016.04.002     Document Type: Review

References (49)

1. 1 Andersen, D.H., Hodges, R.G., Celiac syndrome; genetics of cystic fibrosis of the pancreas, with a consideration of etiology. Am J Dis Child 72 (1946), 62–80.
2. 2 Botstein, D., White, R.L., Skolnick, M., et al. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 32 (1980), 314–331.
3. 3 Quinton, P.M., Chloride impermeability in cystic fibrosis. Nature 301 (1983), 421–422.
4. 4 Kerem, B., Rollins, B.M., Tarran, R., Identification of the cystic fibrosis gene: genetic analysis. Science 245 (1989), 1073–1080.
5. 5 Riordan, J.R., Rommens, J.M., Kerem, B., et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245 (1989), 1066–1073.
6. 6 Rommens, J.M., Iannuzzi, M.C., Kerem, B., et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245 (1989), 1059–1065.
7. 7 Cutting, G.R., Antonarakis, S.E., Buetow, K.H., et al. Analysis of DNA polymorphism haplotypes linked to the cystic fibrosis locus in North American black and Caucasian families supports the existence of multiple mutations of the cystic fibrosis gene. Am J Hum Genet 44 (1989), 307–318.
8. 8 Cutting, G.R., Kasch, L.M., Rosenstein, B.J., et al. A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. Nature 346 (1990), 366–369.
9. 9 Cystic Fibrosis Mutation Database. Available at: http://www.genet.sickkids.on.ca/app. Accessed January 7, 2016.
10. 10 Rohlfs, E.M., Zhou, Z., Sugarman, E.A., et al. The I148T CFTR allele occurs on multiple haplotypes: a complex allele is associated with cystic fibrosis. Genet Med 4 (2002), 319–323.
11. 11 CFTR2@Johns Hopkins - Home Page. Available at: http://cftr2.org/. Accessed January 7, 2016.
12. 12 McKone, E.F., Velentgas, P., Swenson, A.J., et al. Association of sweat chloride concentration at time of diagnosis and CFTR genotype with mortality and cystic fibrosis phenotype. J Cyst Fibros 14 (2015), 580–586.
13. 13 Sosnay, P.R., Siklosi, K.R., Van Goor, F., et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet 45 (2013), 1160–1167.
14. 14 Farrell, P.M., Rosenstein, B.J., White, T.B., et al. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. J Pediatr 153 (2008), S4–S14.
15. 15 Tsui, L.-C., Romeo, G., Greger, R., et al. The identification of the CF (cystic fibrosis) gene: recent progress and new research strategies. 2013, Springer Science & Business Media Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682659/?page=1.
16. 16 Beaudet, A.L., Tsui, L.C., A suggested nomenclature for designating mutations. Hum Mutat 2 (1993), 245–248.
17. 17 Bobadilla, J.L., Macek, M., Fine, J.P., et al. Cystic fibrosis: a worldwide analysis of CFTR mutations–correlation with incidence data and application to screening. Hum Mutat 19 (2002), 575–606.
18. 18 Schrijver, I., Pique, L., Graham, S., et al. The spectrum of CFTR variants in nonwhite cystic fibrosis patients: implications for molecular diagnostic testing. J Mol Diagn 18 (2016), 39–50.
19. 19 Baker, M.W., Atkins, A.E., Cordovado, S.K., et al. Improving newborn screening for cystic fibrosis using next-generation sequencing technology: a technical feasibility study. Genet Med 18:3 (2015), 231–238.
20. 20 Gurwitz, D., Corey, M., Francis, P.W., et al. Perspectives in cystic fibrosis. Pediatr Clin North Am 26 (1979), 603–615.
21. 21 Gaskin, K., Gurwitz, D., Durie, P., et al. Improved respiratory prognosis in patients with cystic fibrosis with normal fat absorption. J Pediatr 100 (1982), 857–862.
22. 22 Kerem, E., Corey, M., Kerem, B.S., et al. The relation between genotype and phenotype in cystic fibrosis–analysis of the most common mutation (delta F508). N Engl J Med 323 (1990), 1517–1522.
23. 23 McKone, E.F., Goss, C.H., Aitken, M.L., CFTR genotype as a predictor of prognosis in cystic fibrosis. Chest 130 (2006), 1441–1447.
24. 24 Green, D.M., McDougal, K.E., Blackman, S.M., et al. Mutations that permit residual CFTR function delay acquisition of multiple respiratory pathogens in CF patients. Respir Res, 11, 2010, 140.
25. 25 Welsh, M.J., Smith, A.E., Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 73 (1993), 1251–1254.
26. 26 Bombieri, C., Seia, M., Castellani, C., Genotypes and phenotypes in cystic fibrosis and cystic fibrosis transmembrane regulator-related disorders. Semin Respir Crit Care Med 36 (2015), 180–193.
27. 27 Bell, S.C., De Boeck, K., Amaral, M.D., New pharmacological approaches for cystic fibrosis: promises, progress, pitfalls. Pharmacol Ther 145 (2015), 19–34.
28. 28 Cutting, G.R., Cystic fibrosis genetics: from molecular understanding to clinical application. Nat Rev Genet 16 (2015), 45–56.
29. 29 Molinski, S.V., Gonska, T., Huan, L.J., et al. Genetic, cell biological, and clinical interrogation of the CFTR mutation c.3700 A>G (p.Ile1234Val) informs strategies for future medical intervention. Genet Med 16 (2014), 625–632.
30. 30 Hinzpeter, A., Aissat, A., Sondo, E., et al. Alternative splicing at a NAGNAG acceptor site as a novel phenotype modifier. PLoS Genet, 6, 2010 Available at: http://www.ncbi.nlm.nih.gov/pubmed/20949073.
31. 31 Elborn, J.S., Personalised medicine for cystic fibrosis: treating the basic defect. Eur Respir Rev 22 (2013), 3–5.
32. 32 Kiesewetter, S., Macek, M. Jr., Davis, C., et al. A mutation in CFTR produces different phenotypes depending on chromosomal background. Nat Genet 5 (1993), 274–278.
33. 33 Chu, C.S., Trapnell, B.C., Curristin, S., et al. Genetic basis of variable exon 9 skipping in cystic fibrosis transmembrane conductance regulator mRNA. Nat Genet 3 (1993), 151–156.
34. 34 Thauvin-Robinet, C., Munck, A., Huet, F., et al. The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening. J Med Genet 46 (2009), 752–758.
35. 35 Cuppens, H., Lin, W., Jaspers, M., et al. Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation. J Clin Invest 101 (1998), 487–496.
36. 36 Sun, W., Anderson, B., Redman, J., et al. CFTR 5T variant has a low penetrance in females that is partially attributable to its haplotype. Genet Med 8 (2006), 339–345.
37. 37 Cystic Fibrosis Foundation, Borowitz, D., Parad, R.B., et al. Cystic Fibrosis Foundation practice guidelines for the management of infants with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome during the first two years of life and beyond. J Pediatr 155 (2009), S106–S116.
38. 38 Munck, A., Mayell, S.J., Winters, V., et al. Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID): a new designation and management recommendations for infants with an inconclusive diagnosis following newborn screening. J Cyst Fibros 14 (2015), 706–713.
39. 39 Bombieri, C., Claustres, M., De Boeck, K., et al. Recommendations for the classification of diseases as CFTR-related disorders. J Cyst Fibros 10:Suppl 2 (2011), S86–S102.
40. 40 Moskowitz, S., Chmiel, J.F., Sternen, D.L., et al. Clinical practice and genetic counseling for cystic fibrosis and CFTR-related disorders. Genet Med 10 (2008), 851–868.
41. 41 Wang, X., Moylan, B., Leopold, D.A., et al. Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population. JAMA 284 (2000), 1814–1819.
42. 42 Wilschanski, M., Dupuis, A., Ellis, L., et al. Mutations in the cystic fibrosis transmembrane regulator gene and in vivo transepithelial potentials. Am J Respir Crit Care Med 174 (2006), 787–794.
43. 43 Masson, E., Chen, J.-M., A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients. PLoS One, 8, 2013, e73522.
44. 44 Gonska, T., Choi, P., Stephenson, A., et al. Role of cystic fibrosis transmembrane conductance regulator in patients with chronic sinopulmonary disease. Chest 142 (2012), 996–1004.
45. 45 Drumm, M.L., Konstan, M.W., Schluchter, M.D., et al. Genetic modifiers of lung disease in cystic fibrosis. N Engl J Med 353 (2005), 1443–1453.
46. 46 Blackman, S.M., Commander, C.W., Watson, C., et al. Genetic modifiers of cystic fibrosis-related diabetes. Diabetes 62 (2013), 3627–3635.
47. 47 Corvol, H., Blackman, S.M., Boëlle, P.Y., et al. Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis. Nat Commun, 6, 2015, 8382.
48. 48 Emond, M.J., Louie, T., Emerson, J., et al. Exome sequencing of phenotypic extremes identifies CAV2 and TMC6 as interacting modifiers of chronic pseudomonas aeruginosa infection in cystic fibrosis. PLoS Genet, 11, 2015, e1005273.
49. 49 Bartlett, J.R., Friedman, K.J., Ling, S.C., et al. Genetic modifiers of liver disease in cystic fibrosis. JAMA 302 (2009), 1076–1083.