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Principles of Molecular Pathology pp 141–184Cite as

Inherited Disorders

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Abstract

The molecular bases of numerous inherited diseases are now known, and diagnostic testing for many of these is now widely available. Molecular testing is performed to establish, confirm, or exclude a diagnosis, for screening, or, in some cases, to predict the severity of disease. Of the many genetic diseases that can be investigated by molecular diagnostic techniques, testing for a few has become relatively commonplace in clinical laboratories. These include cystic fibrosis, hereditary hemochromatosis, certain thrombophilias, Huntington’s disease, and fragile X syndrome. In this chapter, the molecular pathology of these diseases is reviewed, as are some of the more common mitochondrial disorders that illustrate the principles of molecular pathology of this group of diseases. In addition, because of the widespread implementation of newborn screening programs in most countries, the molecular bases of diseases that are commonly included in these programs are also described.

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References

  1. Hamosh A, Fitz-Simmons SC, Macek M Jr, Knowles MR, Rosenstein BJ, Cutting GR. Comparison of the clinical manifestations of cystic fibrosis in black and white patients. J Pediatr 1998; 132: 255 - 9.

    Article  PubMed  CAS  Google Scholar 

  2. Doull IJ. Recent advances in cystic fibrosis. Arch Dis Child 2001; 85: 62 - 6.

    Article  PubMed  CAS  Google Scholar 

  3. Bals R, Weiner DJ, Wilson JM. The innate immune system in cystic fibrosis lung disease. J Clin Invest 1999; 103: 303 - 7.

    Article  PubMed  CAS  Google Scholar 

  4. Webb AK, Egan J. Should patients with cystic fibrosis infected with Burkholderia cepacia undergo lung transplantation? Thorax 1997; 52: 671 - 3.

    Article  PubMed  CAS  Google Scholar 

  5. Tummler B, Kiewitz C. Cystic fibrosis: an inherited susceptibility to bacterial respiratory infections. Mol Med Today 1999; 5: 351 - 8.

    Article  PubMed  CAS  Google Scholar 

  6. Ramachandran C, Melnick SJ. Multidrug resistance in human tumors—molecular diagnosis and clinical significance. Mol Diagn 1999; 4: 81 - 94.

    Article  PubMed  CAS  Google Scholar 

  7. Ashcroft FM, Gribble FM. New windows on the mechanism of action of K(ATP) channel openers. Trends Pharmacol Sci 2000; 21: 439 - 45.

    Article  PubMed  CAS  Google Scholar 

  8. Wine JJ. The genesis of cystic fibrosis lung disease. J Clin Invest 1999; 103: 309 - 12.

    Article  PubMed  CAS  Google Scholar 

  9. Hanrahan JW. Airway plumbing. J Clin Invest 2000; 105: 1343 - 4.

    Article  PubMed  CAS  Google Scholar 

  10. Stern RC. The diagnosis of cystic fibrosis. N Engl J Med 1997; 336: 487 - 91.

    Article  PubMed  CAS  Google Scholar 

  11. Schwiebert EM, Benos DJ, Fuller CM. Cystic fibrosis: a multiple exocrinopathy caused by dysfunctions in a multifunctional transport protein. Am J Med 1998; 104: 576 - 90.

    Article  PubMed  CAS  Google Scholar 

  12. Zeitlin PL. Advances in the diagnosis of cystic fibrosis in infants. J Pediatr 2001; 139: 345 - 6.

    Article  PubMed  CAS  Google Scholar 

  13. Rosenstein BJ, Cutting GR. The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr 1998; 132: 589 - 95.

    Article  PubMed  CAS  Google Scholar 

  14. Farrell PM, Kosorok MR, Rock MJ, et al. Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Wisconsin Cystic Fibrosis Neonatal Screening Study Group. Pediatrics 2001; 107: 1 - 13.

    Article  PubMed  CAS  Google Scholar 

  15. http://www.genet.sickkids.on.ca/cftr/.

    Google Scholar 

  16. Abeliovich D, Lavon IP, Lerer I, et al. Screening for five mutations detects 97% of cystic fibrosis (CF) chromosomes and predicts a carrier frequency of 1:29 in the Jewish Ashkenazi population. Am J Hum Genet 1992; 51: 951 - 6.

    PubMed  CAS  Google Scholar 

  17. 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 - 80.

    Article  PubMed  CAS  Google Scholar 

  18. Daudin M, Bieth E, Bujan L, Massat G, Pontonnier F, Mieusset R. Congenital bilateral absence of the vas deferens: clinical characteristics, biological parameters, cystic fibrosis transmembrane conductance regulator gene mutations, and implications for genetic counseling. Fertil Steril 2000; 74: 1164 - 74.

    Article  PubMed  CAS  Google Scholar 

  19. Kim ED, Bischoff FZ, Lipshultz LI, Lamb DJ. Genetic concerns for the subfertile male in the era of ICSI. Prenat Diagn 1998; 18: 1349 - 65.

    Article  PubMed  CAS  Google Scholar 

  20. Cohn JA, Friedman KJ, Noone PG, Knowles MR, Silverman LM, Jowell PS. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. N Engl J Med 1998; 339: 653 - 8.

    Article  PubMed  CAS  Google Scholar 

  21. Girodon E, Cazeneuve C, Lebargy F, et al. CFTR gene mutations in adults with disseminated bronchiectasis. Eur J Hum Genet 1997; 5: 149 - 55.

    PubMed  CAS  Google Scholar 

  22. 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.

    PubMed  CAS  Google Scholar 

  23. Mickle JE, Cutting GR. Genotype-phenotype relationships in cystic fibrosis. Med Clin North Am 2000; 84: 597 - 607.

    Article  PubMed  CAS  Google Scholar 

  24. LeGrys VA. Assessment of sweat-testing practices for the diagnosis of cystic fibrosis. Arch Pathol Lab Med 2001; 125: 1420 - 4.

    Google Scholar 

  25. Crossley JR, Elliott RB, Smith PA. Dried-blood spot screening for cystic fibrosis in the newborn. Lancet 1979; 1: 472 - 4.

    Article  PubMed  CAS  Google Scholar 

  26. Gregg RG, Simantel A, Farrell PM, et al. Newborn screening for cystic fibrosis in Wisconsin: comparison of biochemical and molecular methods. Pediatrics 1997; 99: 819 - 24.

    Article  PubMed  CAS  Google Scholar 

  27. Ranieri E, Lewis BD, Gerace RL, et al. Neonatal screening for cystic fibrosis using immunoreactive trypsinogen and direct gene analysis: four years’ experience. BMJ 1994; 308: 1469 - 72.

    CAS  Google Scholar 

  28. Wilcken B, Wiley V, Sherry G, Bayliss U. Neonatal screening for cystic fibrosis: a comparison of two strategies for case detection in 1.2 million babies. J Pediatr 1995; 127: 965 - 70.

    Article  PubMed  CAS  Google Scholar 

  29. Lester LA, Kraut J, Lloyd-Still J, et al. Delta F508 genotype does not predict disease severity in an ethnically diverse cystic fibrosis population. Pediatrics 1994; 93: 114 - 8.

    PubMed  CAS  Google Scholar 

  30. Spence JE, Perciaccante RG, Greig GM, et al. Uniparental disomy as a mechanism for human genetic disease. Am J Hum Genet 1988; 42: 217 - 26.

    PubMed  CAS  Google Scholar 

  31. Grody WW, Cutting GR, Klinger KW, Richards CS, Watson MS, Desnick RJ. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet Med 2001; 3: 149 - 54.

    Article  PubMed  CAS  Google Scholar 

  32. Andrews NC. Disorders of iron metabolism. N Engl J Med 1999; 341: 1986 - 95.

    Article  PubMed  CAS  Google Scholar 

  33. Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996; 13: 399 - 408.

    Article  PubMed  CAS  Google Scholar 

  34. Feder JN, Penny DM, Irrinki A, et al. The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. Proc Natl Acad Sci USA 1998; 95: 1472 - 7.

    Article  PubMed  CAS  Google Scholar 

  35. Waheed A, Parkkila S, Zhou XY, et al. Hereditary hemochromatosis: effects of C282Y and H63D mutations on association with beta2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells. Proc Natl Acad Sci USA 1997; 94: 12384 - 9.

    Article  PubMed  CAS  Google Scholar 

  36. Ajioka RS, Jorde LB, Gruen JR, et al. Haplotype analysis of hemochromatosis: evaluation of different linkage-disequilibrium approaches and evolution of disease chromosomes. Am J Hum Genet 1997; 60: 1439 - 47.

    Article  PubMed  CAS  Google Scholar 

  37. Lyon E, Frank EL. Hereditary hemochromatosis since discovery of the HFE gene. Clin Chem 2001; 47: 1147 - 56.

    PubMed  CAS  Google Scholar 

  38. Bacon BR, Sadiq SA. Hereditary hemochromatosis: presentation and diagnosis in the 1990s. Am J Gastroenterol 1997; 92: 784 - 9.

    PubMed  CAS  Google Scholar 

  39. Witte DL, Crosby WH, Edwards CQ, Fairbanks VF, Mitros FA. Practice guideline development task force of the College of American Pathologists. Hereditary hemochromatosis. Clin Chim Acta 1996; 245: 139 - 200.

    Article  PubMed  Google Scholar 

  40. Reyes M, Blanck HM, Khoury MJ. Screening for iron overload due to hereditary hemochromatosis. 2002. http://www.cdc.gov/nccdphp/dnpa/hemochromatosis/ screening.htm

    Google Scholar 

  41. American Hemochromatosis Society. Guidelines for screening, diagnosis, treatment and management of patients with hereditary hemochromatosis/iron overload. 2000. http://www.americanhs.org/2000guidelines.htm

    Google Scholar 

  42. Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353: 1167 - 73.

    Article  PubMed  CAS  Google Scholar 

  43. Zivelin A, Griffin JH, Xu X, et al. A single genetic origin for a common Caucasian risk factor for venous thrombosis. Blood 1997; 89: 397 - 402.

    PubMed  CAS  Google Scholar 

  44. Press RD, Bauer KA, Kujovich JL, Heit JA. Clinical utility of factor V leiden (R506Q) testing for the diagnosis and management of thromboembolic disorders. Arch Pathol Lab Med 2002; 126: 1304 - 18.

    PubMed  Google Scholar 

  45. Emmerich J, Rosendaal FR, Cattaneo M, et al. Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism—pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism. Thromb Haemost 2001; 86: 809 - 16.

    PubMed  CAS  Google Scholar 

  46. Bernardi F, Faioni EM, Castoldi E, et al. A factor V genetic component differing from factor V R506Q contributes to the activated protein C resistance phenotype. Blood 1997; 90: 1552 - 7.

    PubMed  CAS  Google Scholar 

  47. Alhenc-Gelas M, Nicaud V, Gandrille S, et al. The factor V gene A4070G mutation and the risk of venous thrombosis. Thromb Haemost 1999; 81: 193 - 7.

    PubMed  CAS  Google Scholar 

  48. Faioni EM, Franchi F, Bucciarelli P, et al. Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (factor V Leiden). Blood 1999; 94: 3062 - 6.

    PubMed  CAS  Google Scholar 

  49. de Visser MC, Guasch JF, Kamphuisen PW, Vos HL, Rosendaal FR, Bertina RM. The HR2 haplotype of factor V: effects on factor V levels, normalized activated protein C sensitivity ratios and the risk of venous thrombosis. Thromb Haemost 2000; 83: 577 - 82.

    PubMed  Google Scholar 

  50. Yamazaki T, Nicolaes GA, Sorensen KW, Dahlback B. Molecular basis of quantitative factor V deficiency associated with factor V R2 haplotype. Blood 2002; 100: 2515 - 21.

    Article  PubMed  CAS  Google Scholar 

  51. Zoller B, Svensson PJ, He X, Dahlback B. Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 1994; 94: 2521 - 4.

    Article  PubMed  CAS  Google Scholar 

  52. Graf LL, Welsh CH, Qamar Z, Marlar RA. Activated protein C resistance assay detects thrombotic risk factors other than factor V Leiden. Am J Clin Pathol 2003; 119: 52 - 60.

    Article  PubMed  CAS  Google Scholar 

  53. Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004 - 8.

    Article  PubMed  CAS  Google Scholar 

  54. Jorquera JI, Montoro JM, Fernandez MA, Aznar JA, Aznar J. Modified test for activated protein C resistance. Lancet 1994; 344: 1162 - 3.

    Article  PubMed  CAS  Google Scholar 

  55. Trossaert M, Conard J, Horellou MH, et al. Modified APC resistance assay for patients on oral anticoagulants. Lancet 1994; 344: 1709.

    Article  PubMed  CAS  Google Scholar 

  56. Tripodi A, Negri B, Bertina RM, Mannucci PM. Screening for the FV:Q506 mutation—evaluation of thirteen plasma-based methods for their diagnostic efficacy in comparison with DNA analysis. Thromb Haemost 1997; 77: 436 - 9.

    PubMed  CAS  Google Scholar 

  57. Tripodi A, Mannucci PM. Laboratory investigation of thrombophilia. Clin Chem 2001; 47: 1597 - 606.

    PubMed  CAS  Google Scholar 

  58. Gehring NH, Frede U, Neu-Yilik G, et al. Increased efficiency of mRNA 3’ end formation: a new genetic mechanism contributing to hereditary thrombophilia. Nat Genet 2001; 28: 389 - 92.

    Article  PubMed  CAS  Google Scholar 

  59. Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698 - 703.

    PubMed  CAS  Google Scholar 

  60. Rosendaal FR, Siscovick DS, Schwartz SM, Psaty BM, Raghunathan TE, Vos HL. A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood 1997; 90: 1747 - 50.

    PubMed  CAS  Google Scholar 

  61. McGlennen RC, Key NS. Clinical and laboratory management of the prothrombin G20210A mutation. Arch Pathol Lab Med 2002; 126: 1319 - 25.

    PubMed  CAS  Google Scholar 

  62. Grody WW, Griffin JH, Taylor AK, Korf BR, Heit JA. American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genet Med 2001; 3: 139 - 48.

    Article  PubMed  CAS  Google Scholar 

  63. Kremer B, Goldberg P, Andrew SE, et al. A worldwide study of the Huntington’s disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med 1994; 330: 1401 - 6.

    Article  PubMed  CAS  Google Scholar 

  64. Falush D, Almqvist EW, Brinkmann RR, Iwasa Y, Hayden MR. Measurement of mutational flow implies both a high new-mutation rate for Huntington disease and substantial underascertainment of late-onset cases. Am J Hum Genet 2001; 68: 373 - 85.

    Article  PubMed  CAS  Google Scholar 

  65. Cummings CJ, Zoghbi HY. Fourteen and counting: unraveling trinucleotide repeat diseases. Hum Mol Genet 2000; 9: 909 - 16.

    Article  PubMed  CAS  Google Scholar 

  66. AnonymousACMG/ASHG statement. Laboratory guidelines for Huntington disease genetic testing. The American College of Medical Genetics/American Society of Human Genetics Huntington Disease Genetic Testing Working Group. Am J Hum Genet 1998; 62: 1243 - 7.

    Article  Google Scholar 

  67. Andrew SE, Goldberg YP, Kremer B, et al. Huntington disease without CAG expansion: phenocopies or errors in assignment? Am J Hum Genet 1994; 54: 852 - 63.

    PubMed  CAS  Google Scholar 

  68. Moore RC, Xiang F, Monaghan J, et al. Huntington disease phenocopy is a familial prion disease. Am J Hum Genet 2001; 69: 1385 - 8.

    Article  PubMed  CAS  Google Scholar 

  69. Nolin SL, Lewis FA 3rd, Ye LL, et al. Familial transmission of the FMR1 CGG repeat. Am J Hum Genet 1996; 59: 1252 - 61.

    PubMed  CAS  Google Scholar 

  70. Darnell JC, Jensen KB, Jin P, Brown V, Warren ST, Darnell RB. Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 2001; 107: 489 - 99.

    Article  PubMed  CAS  Google Scholar 

  71. Brown V, Jin P, Ceman S, et al. Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 2001; 107: 477 - 87.

    Article  PubMed  CAS  Google Scholar 

  72. Maddalena A, Richards CS, McGinniss MJ, et al. Technical standards and guidelines for fragile X: the first of a series of disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics. Quality Assurance Subcommittee of the Laboratory Practice Committee. Genet Med 2001; 3: 200 - 5.

    Article  PubMed  CAS  Google Scholar 

  73. Prezant TR, Agapian JV, Bohlman MC, et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet 1993; 4: 289 - 94.

    Article  PubMed  CAS  Google Scholar 

  74. Ashizawa T, Subramony SH. What is Kearns-Sayre syndrome after all? Arch Neurol 2001; 58: 1053 - 4.

    Article  PubMed  CAS  Google Scholar 

  75. Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell 1990; 61: 931 - 7.

    Article  PubMed  CAS  Google Scholar 

  76. Shoffner JM, Wallace DC. Mitochondrial genetics: principles and practice. Am J Hum Genet 1992; 51: 1179 - 86.

    PubMed  CAS  Google Scholar 

  77. Lam CW, Lau CH, Williams JC, Chan YW, Wong LJ. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) triggered by valproate therapy. Eur J Pediatr 1997; 156: 562 - 4.

    Article  PubMed  CAS  Google Scholar 

  78. Goto Y, Nonaka I, Horai S. A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 1990; 348: 651 - 3.

    Article  PubMed  CAS  Google Scholar 

  79. Goto Y, Nonaka I, Horai S. A new mtDNA mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Biochim Biophys Acta 1991; 1097: 238 - 40.

    Article  PubMed  CAS  Google Scholar 

  80. Evidente VG, Gwinn-Hardy KA, Caviness JN, Gilman S. Hereditary ataxias. Mayo Clin Proc 2000; 75: 475 - 90.

    PubMed  CAS  Google Scholar 

  81. Pandolfo M. Molecular pathogenesis of Friedreich ataxia. Arch Neurol 1999; 56: 1201 - 8.

    Article  PubMed  CAS  Google Scholar 

  82. Levy HL. Newborn screening by tandem mass spectrometry: a new era. Clin Chem 1998; 44: 2401 - 2.

    PubMed  CAS  Google Scholar 

  83. Murphy M, McHugh B, Tighe O, et al. Genetic basis of transferase-deficient galactosaemia in Ireland and the population history of the Irish Travellers. Eur J Hum Genet 1999; 7: 549 - 54.

    Article  PubMed  CAS  Google Scholar 

  84. Aoki K, Wada Y. Outcome of the patients detected by newborn screening in Japan. Acta Paediatr Jpn 1988; 30: 429 - 34.

    Article  PubMed  CAS  Google Scholar 

  85. Suzuki M, West C, Beutler E. Large-scale molecular screening for galactosemia alleles in a pan-ethnic population. Hum Genet 2001; 109: 210 - 5.

    Article  PubMed  CAS  Google Scholar 

  86. Elsas LJ, Lai K, Saunders CJ, Langley SD. Functional analysis of the human galactose-1-phosphate uridyltransferase promoter in Duarte and LA variant galactosemia. Mol Genet Metab 2001; 72: 297 - 305.

    Article  PubMed  CAS  Google Scholar 

  87. Hunter M, Angelicheva D, Levy HL, Pueschel SM, Kalaydjieva L. Novel mutations in the GALK1 gene in patients with galactokinase deficiency. Hum Mutat 2001; 17: 77 - 8.

    Article  PubMed  CAS  Google Scholar 

  88. Walter JH, Roberts RE, Besley GT, et al. Generalised uridine diphosphate galactose-4-epimerase deficiency. Arch Dis Child 1999; 80: 374 - 6.

    Article  PubMed  CAS  Google Scholar 

  89. Wohlers TM, Christacos NC, Harreman MT, Fridovich-Keil JL. Identification and characterization of a mutation, in the human UDP-galactose-4-epimerase gene, associated with generalized epimerase-deficiency galactosemia. Am J Hum Genet 1999; 64: 462 - 70.

    Article  PubMed  CAS  Google Scholar 

  90. Macchia PE, Lapi P, Krude H, et al. PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis. Nat Genet 1998; 19: 83 - 6.

    Article  PubMed  CAS  Google Scholar 

  91. Macchia PE. Recent advances in understanding the molecular basis of primary congenital hypothyroidism. Mol Med Today 2000; 6: 36 - 42.

    Article  PubMed  CAS  Google Scholar 

  92. Kopp P. Perspective: genetic defects in the etiology of congenital hypothyroidism. Endocrinology 2002; 143: 2019 - 24.

    Article  PubMed  CAS  Google Scholar 

  93. Utiger RD. Thyrotropin-receptor mutations and thyroid dysfunction. N Engl J Med 1995; 332: 183 - 5.

    Article  PubMed  CAS  Google Scholar 

  94. Sunthornthepvarakui T, Gottschalk ME, Hayashi Y, Refetoff S. Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene. N Engl J Med 1995; 332: 155 - 60.

    Article  PubMed  CAS  Google Scholar 

  95. Anonymous. Population variation of common cystic fibrosis mutations. The Cystic Fibrosis Genetic Analysis Consortium. Hum Mutat 1994; 4: 167 - 77.

    Article  Google Scholar 

  96. Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJ. Global prevalence of putative haemochromatosis mutations. J Med Genet 1997; 34: 275 - 8.

    Article  PubMed  CAS  Google Scholar 

  97. Steinberg KK, Cogswell ME, Chang JC, et al. Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States. JAMA 2001; 285: 2216 - 22.

    CAS  Google Scholar 

  98. Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med 2001; 344: 1222 - 31.

    Article  PubMed  CAS  Google Scholar 

  99. Nowacki PM, Byck S, Prevost L, Scriver CR. PAH Mutation Analysis Consortium Database: 1997. Prototype for relational locus-specific mutation databases. Nucleic Acids Res 1998; 26: 220 - 5.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    Anthony A. Killeen MB, BCh, PhD

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Killeen, A.A. (2004). Inherited Disorders. In: Principles of Molecular Pathology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-431-3_5

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  • DOI: https://doi.org/10.1007/978-1-59259-431-3_5

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