#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Current Diagnostic Strategies and Overview of Preimplantation, Prenatal and Postnatal DNA Diagnostics of Cystic Fibrosis in the Czech Republic


Authors: M. Balaščaková 1*;  T. Piskáčková 1*;  A. Holubová 1;  E. Raušová 1;  V. Kazárová 1;  A. Krebsová 1;  M. Koudová 1;  A. Štambergová 1;  J. Čamajová 1;  P. Norambuena 1;  P. Křenková 1;  F. Votava 2;  V. Skalická 3;  V. Vávrová 3;  M. Macek st. 1;  M. Macek ml. 1
Authors‘ workplace: Ústav biologie a lékařské genetiky UK 2. LF a FN Motol, Praha přednosta prof. MUDr. M. Macek ml., DrSc. 1;  Klinika dětí a dorostu UK 3. LF a FN Královské Vinohrady, Praha přednosta doc. MUDr. F. Votava, PhD. 2;  Pediatrická klinika UK 2. LF a FN Motol, Praha přednosta prof. MUDr. J. Lebl, CSc. 3
Published in: Čes-slov Pediat 2008; 63 (2): 62-75.

Overview

Cystic fibrosis (CF) is the most common autosomal recessive and potentially lethal disorder, caused by mutations in the CFTR gene. The disease’s incidence has been estimated to approximately 1 per 2700–3800 newborns in the Czech Republic, which means that every 26th–33rd individual is a healthy carrier of a mutation in the CFTR gene. Early diagnosis by the first two months of life is considered as a favourable prognostic factor. Moreover, a reliable molecular genetic analysis is able to confirm clinical diagnosis of CF. Subsequently, specialised genetic counselling is recommended. The aim of genetic counselling in CF is to provide comprehensible information about the heredity of this disease and to offer carrier testing in direct family members and/or relatives of the index case. Within the frame of preconception care we inform couples about the possibilities of CF prenatal diagnosis. The main purpose of the molecular genetic examination is to provide a choice of a healthy child, not affected by CF.

Key words:
cystic fibrosis (OMIM 219700), CFTR gene, prenatal diagnosis, postnatal diagnosis, newborn screening, mutations, variants, genetic modifiers, preimplantation genetic diagnosis


Sources

1. Davis PB. Cystic fibrosis since 1938. Am. J. Respir. Crit. Care Med. 2006;173:475–482. American College of Medical Genetics, 2006 ed.: Technical Standards and Guidelines for CFTR Mutation Trstiny, http://www.acmg.net/Pages/ACMG_Activities/stds-2002/cf.htm.

2. Welsh MJ, Ramsey BW, Accurso F, Cutting GR. Cystic fibrosis. In Scriver CR, Beaudet AL, Sly WS, Valle D (eds). The Metabolic and Molecular Basis of Inherited Disease. 8th ed. New York: McGraw-Hill, 2001: 5121–5188.

3. Cutting GR. Cystic fibrosis In Rimoin DL, Connor JM, Pyeritz RD (eds). Principles and Practice of Medical Genetics. New York: Churchill Livingstone, 1997: 2685–2717.

4. Vávrová V, a kol. Cystická fibróza. Praha: Grada, 2006.

5. Kosorok MR, Wei W, Farrel PM. The incidence of cystic fibrosis. Statistics in Medicine 1997;15: 449–462.

6. Houštěk J, Vávrová V. K výskytu cystické fibrosy pankreatu v ČSSR. Čs. Pediat. 1962;17: 445–451.

7. Holubová A, Balaščáková M, Skalická V, et al. Novorozenecký screening cystické fibrózy v České republice – závěry pilotní studie. Čes.-slov. Pediat. 2007;62(4): 187–195.

8. Southern K, Munck A, Pollitt R, et al. A survey of newborn screening for cystic fibrosis in Europe. Journal of Cystic Fibrosis 2007;6: 57–65.

9. Dequeker E, Cassiman JJ. Evaluation of CFTR gene mutation testing methods in 136 diagnostic laboratories: report of a large European external quality assessment. Eur. J. Hum. Genet. 1998;6: 165–175.

10. Dequeker E, Cuppens H, Dodge J, et al. Recommendations for quality improvement in genetic testing for cystic fibrosis European Concerted Action on Cystic Fibrosis. Eur. J. Hum. Genet. 2000;8: S2–S24.

11. Girodon Boulandet E, Cazeneuve C, Goossens M. Screening practices in the CFTR gene ABCC7. Hum. Mutat. 2000;15: 135–149.

12. Zielenski J, Rozmahel R, Bozon D, et al. Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Genomics 1991;10: 214–228.

13. Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989;245: 1073–1080.

14. Riordan JR, Rommens JM, Kerem B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 1989;245: 1066–1073.

15. Rommens JM, Iannuzzi MC, Kerem B, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 1989;245: 1059–1065.

16. Bobadilla JL, Macek M Jr, Fine JP, Farell P. Cystic fibrosis: a worldwide analysis of CFTR mutations – correlations with incidence data and application to screening. Hum. Mutat. 2002;19: 575–606.

17. The Molecular Genetic Epidemiology of Cystic Fibrosis. Report of a joint meeting of WHO/ECFTN/ICF (M)A/ECFS http://www.who.int/genomics/publications/ en/ and WHO Geneva, Human Genetics Programme WHO/HGN/CF/WG/04.02.

18. Serre JL, Simon-Bouy B, Mornet E, et al. Studies of RFLP closely linked to the cystic fibrosis locus throughout Europe lead to new considerations in population genetics. Am. J. Hum. Genet. 1990;84: 449–454.

19. Zielenski J. Genotype and phenotype in cystic fibrosis. Respiration 2000;67: 117–133.

20. Mickle JE, Cutting GR. Genotypephenotype relationships in cystic fibrosis. Med. Clin. North Am. 2000;84: 597–607.

21. Rave-Harel N, Kerem E, Nissim-Rafinia M, et al. The molecular basis of partial penetrance of splicing mutations in cystic fibrosis. Am. J. Hum. Genet. 1997;60: 87–94.

22. Audrezet MP, Chen JM, Raguenes O, et al. Genomic rearrangements in the CFTR gene: extensive allelic heterogeneity and diverse mutational mechanisms. Hum. Mutat. 2004;23: 343–357.

23. Ferec C, Casals T, Chuzhanova N, et al. Gross genomic rearrangements involving deletions in the CFTR gene: characterization of six new events from a large cohort of hitherto unidentified cystic fibrosis chromosomes and meta-analysis of the underlying mechanisms. Eur. J. Hum. Genet. 2006;14: 567–576.

24. Morral N, Bertranpetit J, Estivill X, et al. The origin of the major cystic fibrosis mutation (delta F508) in European populations. Nat. Genet. 1994;7: 169–175.

25. Modiano G, Ciminelli BM, Pignatti PF. Cystic fibrosis: Cystic fibrosis and lactase persistence: a possible correlation. Eur. J. Hum. Genet. 2007;15: 255–259.

26. Chiba-Falek O, Parad RB, Kerem E, Kerem B. Variable levels of normal RNA in different fetal organs carrying a cystic fibrosis transmembrane conductance regulator splicing mutation. Am. J. Respir. Crit. Care Med. 1999;159: 1998–2002.

27. Vanscoy LL, Blackman SM, Collaco JM, et al. Heritability of lung disease severity in cystic fibrosis. Am. J. Respir. Crit. Care Med. 2007;175: 1036–1043.

28. Macek M Jr, Krebsová A, Macek M, et al. Current possibilities of prenatal and postnatal molecular genetic diagnosis of cystic fibrosis in Czech and Slovak Republics. Čes.-slov. Pediat. 1997;52: 557–564.

29. Lucarelli M, Narzi L, Piergentili R, et al. A 96-well formatted method for exon and exon/intron boundary full sequencing of the CFTR gene. Anal. Biochem. 2006;353: 226–235.

30. McGinniss MJ, Chen C, Redman JB, et al. Extensive sequencing of the CFTR gene: lessons learned from the first 157 patient samples. Hum. Genet. 2005;118: 331–338.

31. Dequeker E, Cassiman JJ. Genetic testing and quality control in diagnostic laboratories. Nat. Genet. 2000;25: 259–260.

32. Pompei F, Ciminelli BM, Bombieri C, et al. Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations. Eur. J. Hum. Genet. 2006;14(1): 85–93.

33. Groman JD, Karczzeski B, Sheridan M, et al. Phenotypic and genetic characterization of patients with features of “nonclassic” forms of cystic fibrosis. J. Pediatr. 2005;146(5): 675–680.

34. Dörk T, Macek M Jr, Mekus F, et al. 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. Hum. Genet. 2000;106: 259–268.

35. Augarten A, Kerem BS, Yahav Y, et al. Mild cystic fibrosis and normal or borderline sweat test in patients with the 3849 + 10 kb C—>T mutation. Lancet 1993;342: 25–26.

36. Highsmith WE, Burch LH, Zhou Z, et al. A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations. N. Engl. J. Med. 1994;331: 974–980.

37. De Braekeleer M, Allard C, Leblanc JP, et al. Genotype-phenotype correlation in cystic fibrosis patients compound heterozygous for the A455E mutation. Hum. Genet. 1997;101(2): 208–211.

38. Macek M Jr, Mackova A, Hamosh A, et al. Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%. Am. J. Hum. Genet. 1997;60: 1122–1127.

39. Burke W, Aitken ML, Chen SH, Scott CR. Variable severity of pulmonary disease in adults with identical cystic fibrosis mutations. Chest 1992;102: 506–509.

40. Rosenstein BJ, Cutting GR. The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J. Pediatr. 1998;132: 589–595.

41. Macek M, Macek M Jr, Krebsová A. Molekulárně genetická diagnostika v prenatální genetické prevenci VVV a chorob. In Hájek Z, Kulovaný E, Macek M (eds). Prenatální diagnostika. Praha: Grada Publishing, 2000.

42. Modiano G, Bombieri C, Ciminelli BM, et al. A large-scale study of the random variability of a coding sequence: a study on the CFTR gene. Eur. J. Hum. Genet. 2005;13: 184–192.

43. Bombieri C, Giorgi S, Carles S, et al. A new approach for identifying non-pathogenic mutations. An analysis of the cystic fibrosis transmembrane regulator gene in normal individuals. Hum. Genet. 2000;106: 172–178.

44. Cuppens H, Teng H, Raeymaekers P, et al. CFTR haplotype backgrounds on normal and mutant CFTR genes. Hum. Mol. Genet. 1994;3: 607–614.

45. Claustres M, Guittard C, Bozon D, et al. Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France. Hum. Mutat. 2000;16: 143–156.

46. Meschede D, Dworniczak B, Behre HM, et al. CFTR gene mutations in men with bilateral ejaculatory-duct obstruction and anomalies of the seminal vesicles. Am. J. Hum. Genet. 1997;61: 1200–1202.

47. Cohn JA, Noone PG, Jowell PS. Idiopathic pancreatitis related to CFTR: complex inheritance and identification of a modifier gene. Review. J. Invest. Med. 2002;50: 247S–255S.

48. Sharer N, Schwartz M, Malone G, et al Mutations in the CF gene in patients with chronic pancreatitis. N. Engl. J. Med. 1998;339: 645–652.

49. Durie P. Pancreatitis and mutations in the cystic fibrosis gene. N. Engl. J. Med. 1998;339: 687–688.

50. Macek M Jr. Molekulárně genetická podstata akutní/chronické pankreatitidy a pankreatická insuficience u cystické fibrózy. In Dítě P, et al. Onemocnění pankreatu. Praha: Galén, 2002: 71–124.

51. Arduino C, Gallo M, Brusco A, et al. Polyvariant mutant CFTR genes in patients with chronic pancreatitis. Clin. Genet. 1999;56: 400–404.

52. Pignatti PF, Bombieri C, Benetazzo M, et al. CFTR gene variant IVS8-5T in disseminated bronchiectasis. Am. J. Hum. Genet. 1996;58(4): 889–892.

53. Hubert D, Fajac I, Bienvenu T, et al. Diagnosis of CF in adults with diffuse bronchiectasis. J. Cyst. Fibros. 2004;3: 203.

54. Bürger J, Macek M Jr, Sturmann M, et al. Genetic influences in the formation of nasal polyps. Lancet 1991;337: 974.

55. Wang X, Moylan B, Leopold DA, et al. Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population. JAMA 2000;284: 1814–1819.

56. Miller PW, Hamosh A, Macek M Jr, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in allergic bronchopulmonary aspergillosis. Am. J. Hum. Genet. 1996;59: 45–51.

57. Castellani C, Lira MG, Frulloni L, et al. Analysis of the entire coding region of the cystic fibrosis transmembrane regulator gene in idiopathic pancreatitis. Hum. Mutat. 2001;18: 166.

58. Niksic M, Romano M, Buratti E, et al. Functional analysis of cis-acting elements regulating the alternative splicing of human CFTR exon 9. Hum. Mol. Genet. 1999;8: 2339–2349.

59. Cuppens H, Lin W, Jaspers M, et al. Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (TG)n locus explains the partial penetrance of the T5 polymorphism as a disease mutation. J. Clin. Invest. 1998;101: 487–496.

60. Disset A, Michot C, Harris A, et al. A T3 allele in the CFTR gene exacerbates exon 9 skipping in vas deferens and epididymal cell lines and is associated with Congenital Bilateral Absence of Vas Deferens (CBAVD). Hum. Mutat. 2005;25: 72–81.

61. Picci L, Cameran M, Scarpa M, et al. TG15 T5 allele in clinically discordant monozygotic twins with cystic fibrosis. Am. J. Med. Genet. 2007;143: 1936–1937.

62. Cuppens H, Teng H, Raeymaekers P, et al. CFTR haplotype backgrounds on normal and mutant CFTR genes. Hum. Mol. Genet. 1994;3: 607.

63. Amaral MD, Clarke LA, Ramalho AS, et al. Quantitative methods for the analysis of CFTR transcripts/splicing variants. J. Cyst. Fibros. 2004;3: 17–23.

64. Ratbi I, Legendre M, Niel F, et al. Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling. Hum. Reprod. 2007;22: 1285–1291.

65. Groman JD, Hefferon TW, Casals T, et al. Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign. Am. J. Hum. Genet. 2004;74: 176–179.

66. Pagani F, Stuani C, Tzetis M, et al. New type of disease causing mutations: the example of the composite exonic regulatory elements of splicing in CFTR exon 12. Hum. Mol. Genet. 2003;12: 1111–1120.

67. Delaney SJ, Rich DP, Thomson SA, et al. Cystic fibrosis transmembrane conductance regulator splice variants are not conserved and fail to produce chloride channels. Nature Genet. 1993;4: 426–431.

68. Chillon M, Casals T, Mercier B, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N. Engl. J. Med. 1995;332: 1475–1480.

69. Grody WW, Pressler T, Madsen HO, et al. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet. Med. 2001;3: 149–154.

70. Kiesewetter S, Macek M Jr, Davis C, et al. A mutation in CFTR produces different phenotypes depending on chromosomal background. Nat. Genet. 1993;5: 274–278.

71. Scotet V, Audrezet MP, Roussey M, et al. Immunoreactive trypsin/DNA newborn screening for cystic fibrosis: Should the R117H variant be included in CFTR mutation panels? Pediatrics 2006;118: 1523–1529.

72. Peckham D, Conway SP, Morton A, et al. Delayed diagnosis of cystic fibrosis associated with R117H on a background of 7T polythymidine tract at intron 8. J. Cyst. Fibros. 2006;5: 63–65.

73. Buller A, Olson S, Redman JB, et al. Frequency of the cystic fibrosis 3199del6 mutation in individuals heterozygous for I148T. Genet. Med. 2004;6:108–109.

74. Rohlfs EM, Zhou Z, Sugarman EA, et al. The I148T CFTR allele occurs on multiple haplotypes: a complex allele is associated with cystic fibrosis. Genet. Med. 2002;4:319–323.

75. Watson MS, Cutting GR, Desnick RJ, et al. Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genet. Med. 2004;6: 387–391.

76. Sims EJ, Clark A, McCormick J, et al. Cystic fibrosis diagnosed after 2 months of age leads to worse outcomes and requires more therapy. Pediatrics 2007;119: 19–28.

77. Macek M, Tomášová H, Hronková J, et al. Changes in gammaglutamyltransferase activity of the amniotic fluid in fetuses with severe disorders of prenatal development. Čs. Pediat. 1988;43: 129–133.

78. Simon-Bouy B, Satre V, Ferec C, et al. Hyperechogenic fetal bowel: a large French collaborative study of 682 cases. Am. J. Med. Genet. 2003;121A(3): 209–213.

79. Keymolen K, Goossens V, De Rycke M, et al. Clinical outcome of preimplantation genetic diagnosis for cystic fibrosis: The Brussels’ experience. Eur. J. Hum. Gen. 2007;15(7): 752–758.

80. Findlay P. Matthews, Quirke P. Preimplantation genetic diagnosis using fluorescent PCR: results and future developments. J. Assist. Reprod. Genet. 1999; 199–206.

81. Dequeker E, Ramsden S, Grody WW, et al. Quality control in molecular genetic testing. Nat. Rev. Genet. 2001;2: 717–723.

82. Heng BC. Reluctance of medical proffesionals inadopting natural-cycle and minimal ovarian stimulation protocols in human clinical assisted reproduction. Reprod. Biomed. Online 2007;15(1): 9–11.

83. Sanchez-Albisua I, Borell-Kost S, Mau-Holzmann UA, et al. Increased frequency of severe major anomalies in children conceived by intracytoplasmic sperm injection. Dev. Med. Child Neurol. 2007;49(2): 129–134.

84. Machatková M, Krebsová A, Smetanová I, et al. Chromosome Y microdeletions in Czech men with severe reproductive disorders. Čas. Lék. čes. 2003;142(11): 670–675.

85. Macek M, Vilímová S, Potužníková P, Macek M Jr, a kol. Využití lékařské genetiky v reprodukční medicíně. Čas. Lék. čes. 2002;141(1):28–34.

86. Ogino S, Wilson RB. Bayesian analysis and risk assessment in genetic counseling and testing. JMD 2004;6(1).

87. Warwick WJ, Hansen LG, Brown IV, et al. Sweat chloride: quantitative patch for collection and measurement. Clin-Lab-Sci. 2001;14(3): 155–159.

88. Drumm ML, Konstan MW, Schluchter MD, et al. Genetic modifiers of lung disease in cystic fibrosis. N. Engl. J. Med. 2005;353: 1443–1453.

89. Garred P, Pressler T, Madsen HO, et al. Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis. J. Clin. Invest. 1999;104: 431–437.

90. Dorfman R, Zielenski J. Genotype/phenotype correlations. In Bush A, Alton E, Davies J, Griesenbach U. (eds). Cystic Fibrosis in the 21st Century: Progress in Respiratory Research. Basel: Karger, 2006: 61–68.

91. Yarden J, Radojkovic D, De Boeck K, et al. Polymorphisms in the mannose binding lectin gene affect the cystic fibrosis pulmonary phenotype. J. Med. Genet. 2004;41: 629–633.

92. Stonebraker JR, Friedman KJ, Ling SC, et al. Genetic modifiers of severe liver disease in cystic fibrosis: a replication study. Ped. Pulmonol. 2007;Suppl. 30: 381.

93. Wilschanski M, Rivlin J, Cohen S, et al. Clinical and genetic risk factors for CF-related liver disease. Pediatr. 1999;103: 52–57.

94. Elborn JS. How can we prevent multisystem complications of cystic fibrosis? Seminars in Respiratory & Critical Care Medicine 2007;28(3): 303–311.

95. Lester LA, Kraut J, Lloyd-Still J, et al. Delta F508 genotype does not predict disease severity in an ethnically diverse cystic fibrosis population. Pediatr. 1994;93: 114–118.

96. McKone EF, Goss CH, Aitken ML. CFTR genotype as a predictor of prognosis in cystic fibrosis. Chest 2006;130: 1441–1447.

97. Koch C, Cuppens H, Rainisio M, et al. European Epidemiologic Registry of Cystic Fibrosis (ERCF): comparison of major disease manifestations between patients with different classes of mutations. Pediatr. Pulmonol. 2001;31: 1–12.

98. Sheridan MB, Fong P, Groman JD, et al. Mutations in the beta subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome. Hum. Mol. Genet. 2005;14: 3493–3498.

99. Groman JD, Meyer ME, Wilmott RW, et al. Variant cystic fibrosis phenotypes in the absence of CFTR mutations. N. Engl. J. Med. 2002;347: 401–407.

100. Mekus F, Ballmann M, Bronsveld I, et al. Cystic-fibrosis-like disease unrelated to the cystic fibrosis transmembrane conductance regulator. Hum. Genet. 1998;102: 582–586.

101. Welsh MJ, Smith AE. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 1993;73: 1251–1254.

102. Wilschanski M, Zielenski J, Markiewicz D, et al. Correlation of sweat chloride concentration with classes of the cystic fibrosis transmembrane conductance regulator gene mutations. J. Pediatr. 1995;127: 705–710.

103. 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. 2006;174: 787–794.

104. Beaudet A, Taji LC. A suggested nomenclature for designating mutations. Hum. Mutat. 1993;2(4): 245–248.

105. Mak V, Jarvi KA, Zielenski J, et al. Higher proportion of intact exon 9 CFTR mRNA in nasal epithelium compared with vas deferens. Hum. Mol. Genet. 1997;6: 2099–2107.

106. Dörk T, Neumann T, Wulbrand U, et al. Intra and extragenic marker haplotypes of CFTR mutations in cystic fibrosis families. Hum. Genet. 1992;88: 417–425.

107. Farrell PM, Rosenstein BJ, White TB, et al. Guidelines for Diagnosis of Cystic Fibrosis in the Era of Newborn Screening: Cystic Fibrosis Foundation Consensus Report. Submitted to J. Pediatr.

Labels
Neonatology Paediatrics General practitioner for children and adolescents
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#