Генетична диагностика при хемофилия А и В – приложение в клиничната практика
Keywords:
хемофилия A, хемофилия B, генетична диагностика
Abstract
Хемофилия А и В са редки вродени, Х-свързани заболявания, причинени от липса или дефицит на коагулационен фактор VIII (FVIII) или IX (FIX). Тежестта на заболяването зависи от степента на намаляването на нивата на FVIII или FIX, което се определя от вида на патогенните варианти в гените, кодиращи двата фактора (ген за F8 и F9).
Молекулярно-генетичният анализ намира широко приложение при наследствените нарушения на кръвосъсирването. Резултатите от генетичния анализ позволяват генетично консултиране на засегнатите семейства и предоставят възможност да се открие връзката между генотипа и фенотипа на болестта. През последните десетилетия генетичният анализ при хемофилия се подобрява значително. Достъпни са множество нови техники и модификации, както и софтуери за анализ, които превръщат генетичния анализ и интерпретацията на данните в по-бързи и по-точни. Напредъкът в стратегиите за откриване на генетични варианти улеснява идентифицирането на патологични варианти при до 97% от пациентите.
References
Blanchette VS, Key NS, Ljung LR, et al. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost 2014; 12: 1935–1939.
Berntorp E, Shapiro AD. Modern haemophilia care. Lancet 2012; 379: 1447–1456.
Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 1961; 190: 372–373.
Harper PS. Mary Lyon and the hypothesis of random X chromosome inactivation. Hum Genet 2011; 130: 169–174.
Fischer K, Ljung R, Platokouki H, et al. Prospective observational cohort studies for studying rare diseases: the European PedNet Haemophilia Registry. Haemophilia 2014; 20: e280-6.
Gomez K, Laffan M, Keeney S, et al. Recommendations for the clinical interpretation of genetic variants and presentation of results to patients with inherited bleeding disorders. A UK Haemophilia Centre Doctors' Organisation Good Practice Paper. Haemophilia 2019; 25: 116–126.
Miller CH, Bean CJ. Genetic causes of haemophilia in women and girls. Haemophilia 2021; 27: e164-e179.
Pavlova A, Brondke H, Musebeck J, et al. Molecular mechanisms underlying hemophilia A phenotype in seven females. J Thromb Haemost 2009; 7: 976–982.
Acquila M, Caprino D, Bicocchi P, et al. A skewed lyonization phenomenon as cause of hemophilia A in a female patient. Blood 1995; 85: 599–600.
Bennett CM, Boye E, Neufeld EJ. Female monozygotic twins discordant for hemophilia A due to nonrandom X-chromosome inactivation. Am J Hematol 2008; 83: 778–780.
Radic CP, Rossetti LC, Abelleyro MM, et al. Phenotype-genotype correlations in hemophilia A carriers are consistent with the binary role of the phase between F8 and X-chromosome inactivation. J Thromb Haemost 2015; 13: 530–539.
Palla R, Peyvandi F, Shapiro AD. Rare bleeding disorders: diagnosis and treatment. Blood 2015; 125: 2052–2061.
Gitschier J, Wood WI, Goralka TM, et al. Characterization of the human factor VIII gene. Nature 1984; 312: 326–330.
Youssoufian H, Wong C, Aronis S, et al. Moderately severe hemophilia A resulting from Glu----Gly substitution in exon 7 of the factor VIII gene. Am J Hum Genet 1988; 42: 867–871.
El-Maarri O, Olek A, Balaban B, et al. Methylation levels at selected CpG sites in the factor VIII and FGFR3 genes, in mature female and male germ cells: implications for male-driven evolution. Am J Hum Genet 1998; 63: 1001–1008.
Oldenburg J, Schroder J, Schmitt C, et al. Small deletion/insertion mutations within poly-A runs of the factor VIII gene mitigate the severe haemophilia A phenotype. Thrombosis and haemostasis 1998; 79: 452–453.
Chatterjee N, Walker GC. Mechanisms of DNA damage, repair, and mutagenesis. Environ Mol Mutagen 2017; 58: 235–263.
Bagnall RD, Waseem N, Green PM, et al. Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A. Blood 2002; 99: 168–174.
Naylor JA, Buck D, Green P, et al. Investigation of the factor VIII intron 22 repeated region (int22h) and the associated inversion junctions. Hum Mol Genet 1995; 4: 1217–1224.
Lakich D, Kazazian, H. H., Jr., Antonarakis SE, et al. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nat Genet 1993; 5: 236–241.
Rossiter JP, Young M, Kimberland ML, et al. Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells. Hum Mol Genet 1994; 3: 1035–1039.
Tavassoli K, Eigel A, Horst J. A deletion/insertion leading to the generation of a direct repeat as a result of slipped mispairing and intragenic recombination in the factor VIII gene. Hum Genet 1999; 104: 435–437.
Vidal F, Farssac E, Tusell J, et al. First molecular characterization of an unequal homologous alu-mediated recombination event responsible for hemophilia. Thrombosis and haemostasis 2002; 88: 12–16.
Briët E, van Leeuwen-Cornelisse IS, van der Vlerk D, et al. Hemofilie B Leyden. Ned Tijdschr Geneeskd 1986; 130: 1324–1327.
Funnell APW, Crossley M. Hemophilia B Leyden and once mysterious cis-regulatory mutations. Trends Genet 2014; 30: 18–23.
Schwaab R, Oldenburg J, Higuchi M, et al. Haemophilia A: carrier detection by DNA analysis. Blut 1988; 57: 85–90.
Lin S-Y, Su Y-N, Hung C-C, et al. Mutation spectrum of 122 hemophilia A families from Taiwanese population by LD-PCR, DHPLC, multiplex PCR and evaluating the clinical application of HRM. BMC Med Genet 2008; 9: 53.
Higuchi M, Kazazian, H. H., Jr., Kasch L, et al. Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene. Proc Natl Acad Sci U S A 1991; 88: 7405–7409.
Rossetti LC, Radic CP, Larripa IB, et al. Genotyping the hemophilia inversion hotspot by use of inverse PCR. Clin Chem 2005; 51: 1154–1158.
Rossetti LC, Radic CP, Larripa IB, et al. Developing a new generation of tests for genotyping hemophilia-causative rearrangements involving int22h and int1h hotspots in the factor VIII gene. J Thromb Haemost 2008; 6: 830–836.
Lu JT, Campeau PM, Lee BH. Genotype-phenotype correlation--promiscuity in the era of next-generation sequencing. N Engl J Med 2014; 371: 593–596.
Sikkema-Raddatz B, Johansson LF, Boer EN de, et al. Targeted next-generation sequencing can replace Sanger sequencing in clinical diagnostics. Hum Mutat 2013; 34: 1035–1042.
Bastida JM, Del Rey M, Lozano ML, et al. Design and application of a 23-gene panel by next-generation sequencing for inherited coagulation bleeding disorders. Haemophilia 2016; 22: 590–597.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17: 405–424.
Bastida JM, González-Porras JR, Jiménez C, et al. Application of a molecular diagnostic algorithm for haemophilia A and B using next-generation sequencing of entire F8, F9 and VWF genes. Thrombosis and haemostasis 2017; 117: 66–74.
Ver Donck F, Downes K, Freson K. Strengths and limitations of high-throughput sequencing for the diagnosis of inherited bleeding and platelet disorders. J Thromb Haemost 2020.
Zhao M, Wang Q, Wang Q, et al. Computational tools for copy number variation (CNV) detection using next-generation sequencing data: features and perspectives. BMC Bioinformatics 2013; 14 Suppl 11: S1.
Wolf SM. The Continuing Evolution of Ethical Standards for Genomic Sequencing in Clinical Care: Restoring Patient Choice. J Law Med Ethics 2017; 45: 333–340.
Ver Donck F, Labarque V, Freson K. Hemostatic phenotypes and genetic disorders. Res Pract Thromb Haemost 2021; 5: e12637.
Pezeshkpoor B, Pavlova A, Oldenburg J, et al. F8 genetic analysis strategies when standard approaches fail. Hamostaseologie 2014; 34: 167–173.
Czogalla KJ, Watzka M, Oldenburg J. VKCFD2 - from clinical phenotype to molecular mechanism. Hamostaseologie 2016; 36: S13-S20.
McLintock C. Women with bleeding disorders: Clinical and psychological issues. Haemophilia 2018; 24 Suppl 6: 22–28.
Lavery S. Preimplantation genetic diagnosis of haemophilia. Br J Haematol 2009; 144: 303–307.
Punt MC, Aalders TH, Bloemenkamp KWM, et al. The experiences and attitudes of hemophilia carriers around pregnancy: A qualitative systematic review. J Thromb Haemost 2020; 18: 1626–1636.
Gillham A, Greyling B, Wessels T-M, et al. Uptake of Genetic Counseling, Knowledge of Bleeding risks and Psychosocial Impact in a South African Cohort of Female Relatives of People with Hemophilia. J Genet Couns 2015; 24: 978–986.
Lippe C von der, Frich JC, Harris A, et al. "It was a lot Tougher than I Thought It would be". A Qualitative Study on the Changing Nature of Being a Hemophilia Carrier. J Genet Couns 2017; 26: 1324–1332.
Kadir RA, Sabin CA, Goldman E, et al. Reproductive choices of women in families with haemophilia. Haemophilia 2000; 6: 33–40.
Laurie AD, Hill AM, Harraway JR, et al. Preimplantation genetic diagnosis for hemophilia A using indirect linkage analysis and direct genotyping approaches. J Thromb Haemost 2010; 8: 783–789.
Ljung RC. Prenatal diagnosis of haemophilia. Haemophilia 1999; 5: 84–87.
Cutler J, Chappell LC, Kyle P, et al. Third trimester amniocentesis for diagnosis of inherited bleeding disorders prior to delivery. Haemophilia 2013; 19: 904–907.
Ljung RC, Sjörin E. Origin of mutation in sporadic cases of haemophilia A. Brit J Haematol 1999; 106: 870–874.
Leuer M, Oldenburg J, Lavergne JM, et al. Somatic mosaicism in hemophilia A: a fairly common event. Am J Hum Genet 2001; 69: 75–87.
Kasper CK, Buzin CH. Mosaics and haemophilia. Haemophilia 2009; 15: 1181–1186.
Lannoy N, Hermans C. Genetic mosaicism in haemophilia: A practical review to help evaluate the risk of transmitting the disease. Haemophilia 2020; 26: 375–383.
Mårtensson A, Tedgård U, Ljung R. Prenatal diagnosis of haemophilia in Sweden now more commonly used for psychological preparation than termination of pregnancy. Haemophilia 2014; 20: 854–858.
Boardman FK, Young PJ, Warren O, et al. The role of experiential knowledge within attitudes towards genetic carrier screening: A comparison of people with and without experience of spinal muscular atrophy. Health Expect 2018; 21: 201–211.
Hudecova I, Jiang P, Davies J, et al. Noninvasive detection of F8 int22h-related inversions and sequence variants in maternal plasma of hemophilia carriers. Blood 2017; 130: 340–347.
van den Berg HM, Fischer K, Carcao M, et al. Timing of inhibitor development in more than 1000 previously untreated patients with severe hemophilia A. Blood 2019; 134: 317–320.
Male C, Andersson NG, Rafowicz A, et al. Inhibitor incidence in an unselected cohort of previously untreated patients with severe hemophilia B: a PedNet study. Haematologica 2020; 106: 123–129.
Astermark J. FVIII inhibitors: pathogenesis and avoidance. Blood 2015; 125: 2045–2051.
Gouw SC, van den Berg HM, Oldenburg J, et al. F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis. Blood 2012.
Oldenburg J, Pavlova A. Genetic risk factors for inhibitors to factors VIII and IX. Haemophilia 2006; 12 Suppl 6: 15–22.
Eckhardt CL, Loomans JI, van Velzen AS, et al. Inhibitor development and mortality in non-severe hemophilia A. J Thromb Haemost 2015; 13: 1217–1225.
Castaman G, Fijnvandraat K. Molecular and clinical predictors of inhibitor risk and its prevention and treatment in mild hemophilia A. Blood 2014; 124: 2333–2336.
Male C, Andersson NG, Rafowicz A, et al. Inhibitor incidence in an unselected cohort of previously untreated patients with severe hemophilia B: a PedNet study. Haematologica 2020; 106: 123–129.
Bardi E, Astermark J. Genetic risk factors for inhibitors in haemophilia A. Eur J Haematol 2015; 94 Suppl 77: 7–10.
Pavlova A, Oldenburg J. Defining severity of hemophilia: more than factor levels. Semin Thromb Hemost 2013; 39: 702–710.
Lee DH, Walker IR, Teitel J, et al. Effect of the Factor V Leiden Mutation on the Clinical Expression of Severe Hemophilia A. Thromb Haemostasis 2000; 83: 387–391.
Preisler B, Pezeshkpoor B, Banchev A, et al. Familial Multiple Coagulation Factor Deficiencies (FMCFDs) in a Large Cohort of Patients-A Single-Center Experience in Genetic Diagnosis. JCM 2021; 10: 347.
Escuriola Ettingshausen C, Halimeh S, Kurnik K, et al. Symptomatic onset of severe hemophilia A in childhood is dependent on the presence of prothrombotic risk factors. Thrombosis and haemostasis 2001; 85: 218–220.
van Dijk K, van der Bom JG, Fischer K, et al. Phenotype of severe hemophilia A and plasma levels of risk factors for thrombosis. J Thromb Haemost 2007; 5: 1062–1064.
Shetty S, Vora S, Kulkarni B, et al. Contribution of natural anticoagulant and fibrinolytic factors in modulating the clinical severity of haemophilia patients. Brit J Haematol 2007; 138: 541–544.
Boylan B, Rice AS, Staercke C de, et al. Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations. J Thromb Haemost 2015; 13: 1036–1042.
Gupta M, Lillicrap D, Stain AM, et al. Therapeutic consequences for misdiagnosis of type 2N von Willebrand disease. Pediatr Blood Cancer 2011; 57: 1081–1083.
Mazurier C, Goudemand J, Hilbert L, et al. Type 2N von Willebrand disease: clinical manifestations, pathophysiology, laboratory diagnosis and molecular biology. Best Pract Res Clin Haematol 2001; 14: 337–347.
Pavlova A, Delev D, Pezeshkpoor B, et al. Haemophilia A mutations in patients with non-severe phenotype associated with a discrepancy between one-stage and chromogenic factor VIII activity assays. Thrombosis and haemostasis 2014; 111: 851–861.
Keeling DM, Sukhu K, Kemball-Cook G, et al. Diagnostic importance of the two-stage factor VIII:C assay demonstrated by a case of mild haemophilia associated with His1954-->Leu substitution in the factor VIII A3 domain. Br J Haematol 1999; 105: 1123–1126.
Berntorp E, Shapiro AD. Modern haemophilia care. Lancet 2012; 379: 1447–1456.
Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 1961; 190: 372–373.
Harper PS. Mary Lyon and the hypothesis of random X chromosome inactivation. Hum Genet 2011; 130: 169–174.
Fischer K, Ljung R, Platokouki H, et al. Prospective observational cohort studies for studying rare diseases: the European PedNet Haemophilia Registry. Haemophilia 2014; 20: e280-6.
Gomez K, Laffan M, Keeney S, et al. Recommendations for the clinical interpretation of genetic variants and presentation of results to patients with inherited bleeding disorders. A UK Haemophilia Centre Doctors' Organisation Good Practice Paper. Haemophilia 2019; 25: 116–126.
Miller CH, Bean CJ. Genetic causes of haemophilia in women and girls. Haemophilia 2021; 27: e164-e179.
Pavlova A, Brondke H, Musebeck J, et al. Molecular mechanisms underlying hemophilia A phenotype in seven females. J Thromb Haemost 2009; 7: 976–982.
Acquila M, Caprino D, Bicocchi P, et al. A skewed lyonization phenomenon as cause of hemophilia A in a female patient. Blood 1995; 85: 599–600.
Bennett CM, Boye E, Neufeld EJ. Female monozygotic twins discordant for hemophilia A due to nonrandom X-chromosome inactivation. Am J Hematol 2008; 83: 778–780.
Radic CP, Rossetti LC, Abelleyro MM, et al. Phenotype-genotype correlations in hemophilia A carriers are consistent with the binary role of the phase between F8 and X-chromosome inactivation. J Thromb Haemost 2015; 13: 530–539.
Palla R, Peyvandi F, Shapiro AD. Rare bleeding disorders: diagnosis and treatment. Blood 2015; 125: 2052–2061.
Gitschier J, Wood WI, Goralka TM, et al. Characterization of the human factor VIII gene. Nature 1984; 312: 326–330.
Youssoufian H, Wong C, Aronis S, et al. Moderately severe hemophilia A resulting from Glu----Gly substitution in exon 7 of the factor VIII gene. Am J Hum Genet 1988; 42: 867–871.
El-Maarri O, Olek A, Balaban B, et al. Methylation levels at selected CpG sites in the factor VIII and FGFR3 genes, in mature female and male germ cells: implications for male-driven evolution. Am J Hum Genet 1998; 63: 1001–1008.
Oldenburg J, Schroder J, Schmitt C, et al. Small deletion/insertion mutations within poly-A runs of the factor VIII gene mitigate the severe haemophilia A phenotype. Thrombosis and haemostasis 1998; 79: 452–453.
Chatterjee N, Walker GC. Mechanisms of DNA damage, repair, and mutagenesis. Environ Mol Mutagen 2017; 58: 235–263.
Bagnall RD, Waseem N, Green PM, et al. Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A. Blood 2002; 99: 168–174.
Naylor JA, Buck D, Green P, et al. Investigation of the factor VIII intron 22 repeated region (int22h) and the associated inversion junctions. Hum Mol Genet 1995; 4: 1217–1224.
Lakich D, Kazazian, H. H., Jr., Antonarakis SE, et al. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nat Genet 1993; 5: 236–241.
Rossiter JP, Young M, Kimberland ML, et al. Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells. Hum Mol Genet 1994; 3: 1035–1039.
Tavassoli K, Eigel A, Horst J. A deletion/insertion leading to the generation of a direct repeat as a result of slipped mispairing and intragenic recombination in the factor VIII gene. Hum Genet 1999; 104: 435–437.
Vidal F, Farssac E, Tusell J, et al. First molecular characterization of an unequal homologous alu-mediated recombination event responsible for hemophilia. Thrombosis and haemostasis 2002; 88: 12–16.
Briët E, van Leeuwen-Cornelisse IS, van der Vlerk D, et al. Hemofilie B Leyden. Ned Tijdschr Geneeskd 1986; 130: 1324–1327.
Funnell APW, Crossley M. Hemophilia B Leyden and once mysterious cis-regulatory mutations. Trends Genet 2014; 30: 18–23.
Schwaab R, Oldenburg J, Higuchi M, et al. Haemophilia A: carrier detection by DNA analysis. Blut 1988; 57: 85–90.
Lin S-Y, Su Y-N, Hung C-C, et al. Mutation spectrum of 122 hemophilia A families from Taiwanese population by LD-PCR, DHPLC, multiplex PCR and evaluating the clinical application of HRM. BMC Med Genet 2008; 9: 53.
Higuchi M, Kazazian, H. H., Jr., Kasch L, et al. Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene. Proc Natl Acad Sci U S A 1991; 88: 7405–7409.
Rossetti LC, Radic CP, Larripa IB, et al. Genotyping the hemophilia inversion hotspot by use of inverse PCR. Clin Chem 2005; 51: 1154–1158.
Rossetti LC, Radic CP, Larripa IB, et al. Developing a new generation of tests for genotyping hemophilia-causative rearrangements involving int22h and int1h hotspots in the factor VIII gene. J Thromb Haemost 2008; 6: 830–836.
Lu JT, Campeau PM, Lee BH. Genotype-phenotype correlation--promiscuity in the era of next-generation sequencing. N Engl J Med 2014; 371: 593–596.
Sikkema-Raddatz B, Johansson LF, Boer EN de, et al. Targeted next-generation sequencing can replace Sanger sequencing in clinical diagnostics. Hum Mutat 2013; 34: 1035–1042.
Bastida JM, Del Rey M, Lozano ML, et al. Design and application of a 23-gene panel by next-generation sequencing for inherited coagulation bleeding disorders. Haemophilia 2016; 22: 590–597.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17: 405–424.
Bastida JM, González-Porras JR, Jiménez C, et al. Application of a molecular diagnostic algorithm for haemophilia A and B using next-generation sequencing of entire F8, F9 and VWF genes. Thrombosis and haemostasis 2017; 117: 66–74.
Ver Donck F, Downes K, Freson K. Strengths and limitations of high-throughput sequencing for the diagnosis of inherited bleeding and platelet disorders. J Thromb Haemost 2020.
Zhao M, Wang Q, Wang Q, et al. Computational tools for copy number variation (CNV) detection using next-generation sequencing data: features and perspectives. BMC Bioinformatics 2013; 14 Suppl 11: S1.
Wolf SM. The Continuing Evolution of Ethical Standards for Genomic Sequencing in Clinical Care: Restoring Patient Choice. J Law Med Ethics 2017; 45: 333–340.
Ver Donck F, Labarque V, Freson K. Hemostatic phenotypes and genetic disorders. Res Pract Thromb Haemost 2021; 5: e12637.
Pezeshkpoor B, Pavlova A, Oldenburg J, et al. F8 genetic analysis strategies when standard approaches fail. Hamostaseologie 2014; 34: 167–173.
Czogalla KJ, Watzka M, Oldenburg J. VKCFD2 - from clinical phenotype to molecular mechanism. Hamostaseologie 2016; 36: S13-S20.
McLintock C. Women with bleeding disorders: Clinical and psychological issues. Haemophilia 2018; 24 Suppl 6: 22–28.
Lavery S. Preimplantation genetic diagnosis of haemophilia. Br J Haematol 2009; 144: 303–307.
Punt MC, Aalders TH, Bloemenkamp KWM, et al. The experiences and attitudes of hemophilia carriers around pregnancy: A qualitative systematic review. J Thromb Haemost 2020; 18: 1626–1636.
Gillham A, Greyling B, Wessels T-M, et al. Uptake of Genetic Counseling, Knowledge of Bleeding risks and Psychosocial Impact in a South African Cohort of Female Relatives of People with Hemophilia. J Genet Couns 2015; 24: 978–986.
Lippe C von der, Frich JC, Harris A, et al. "It was a lot Tougher than I Thought It would be". A Qualitative Study on the Changing Nature of Being a Hemophilia Carrier. J Genet Couns 2017; 26: 1324–1332.
Kadir RA, Sabin CA, Goldman E, et al. Reproductive choices of women in families with haemophilia. Haemophilia 2000; 6: 33–40.
Laurie AD, Hill AM, Harraway JR, et al. Preimplantation genetic diagnosis for hemophilia A using indirect linkage analysis and direct genotyping approaches. J Thromb Haemost 2010; 8: 783–789.
Ljung RC. Prenatal diagnosis of haemophilia. Haemophilia 1999; 5: 84–87.
Cutler J, Chappell LC, Kyle P, et al. Third trimester amniocentesis for diagnosis of inherited bleeding disorders prior to delivery. Haemophilia 2013; 19: 904–907.
Ljung RC, Sjörin E. Origin of mutation in sporadic cases of haemophilia A. Brit J Haematol 1999; 106: 870–874.
Leuer M, Oldenburg J, Lavergne JM, et al. Somatic mosaicism in hemophilia A: a fairly common event. Am J Hum Genet 2001; 69: 75–87.
Kasper CK, Buzin CH. Mosaics and haemophilia. Haemophilia 2009; 15: 1181–1186.
Lannoy N, Hermans C. Genetic mosaicism in haemophilia: A practical review to help evaluate the risk of transmitting the disease. Haemophilia 2020; 26: 375–383.
Mårtensson A, Tedgård U, Ljung R. Prenatal diagnosis of haemophilia in Sweden now more commonly used for psychological preparation than termination of pregnancy. Haemophilia 2014; 20: 854–858.
Boardman FK, Young PJ, Warren O, et al. The role of experiential knowledge within attitudes towards genetic carrier screening: A comparison of people with and without experience of spinal muscular atrophy. Health Expect 2018; 21: 201–211.
Hudecova I, Jiang P, Davies J, et al. Noninvasive detection of F8 int22h-related inversions and sequence variants in maternal plasma of hemophilia carriers. Blood 2017; 130: 340–347.
van den Berg HM, Fischer K, Carcao M, et al. Timing of inhibitor development in more than 1000 previously untreated patients with severe hemophilia A. Blood 2019; 134: 317–320.
Male C, Andersson NG, Rafowicz A, et al. Inhibitor incidence in an unselected cohort of previously untreated patients with severe hemophilia B: a PedNet study. Haematologica 2020; 106: 123–129.
Astermark J. FVIII inhibitors: pathogenesis and avoidance. Blood 2015; 125: 2045–2051.
Gouw SC, van den Berg HM, Oldenburg J, et al. F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis. Blood 2012.
Oldenburg J, Pavlova A. Genetic risk factors for inhibitors to factors VIII and IX. Haemophilia 2006; 12 Suppl 6: 15–22.
Eckhardt CL, Loomans JI, van Velzen AS, et al. Inhibitor development and mortality in non-severe hemophilia A. J Thromb Haemost 2015; 13: 1217–1225.
Castaman G, Fijnvandraat K. Molecular and clinical predictors of inhibitor risk and its prevention and treatment in mild hemophilia A. Blood 2014; 124: 2333–2336.
Male C, Andersson NG, Rafowicz A, et al. Inhibitor incidence in an unselected cohort of previously untreated patients with severe hemophilia B: a PedNet study. Haematologica 2020; 106: 123–129.
Bardi E, Astermark J. Genetic risk factors for inhibitors in haemophilia A. Eur J Haematol 2015; 94 Suppl 77: 7–10.
Pavlova A, Oldenburg J. Defining severity of hemophilia: more than factor levels. Semin Thromb Hemost 2013; 39: 702–710.
Lee DH, Walker IR, Teitel J, et al. Effect of the Factor V Leiden Mutation on the Clinical Expression of Severe Hemophilia A. Thromb Haemostasis 2000; 83: 387–391.
Preisler B, Pezeshkpoor B, Banchev A, et al. Familial Multiple Coagulation Factor Deficiencies (FMCFDs) in a Large Cohort of Patients-A Single-Center Experience in Genetic Diagnosis. JCM 2021; 10: 347.
Escuriola Ettingshausen C, Halimeh S, Kurnik K, et al. Symptomatic onset of severe hemophilia A in childhood is dependent on the presence of prothrombotic risk factors. Thrombosis and haemostasis 2001; 85: 218–220.
van Dijk K, van der Bom JG, Fischer K, et al. Phenotype of severe hemophilia A and plasma levels of risk factors for thrombosis. J Thromb Haemost 2007; 5: 1062–1064.
Shetty S, Vora S, Kulkarni B, et al. Contribution of natural anticoagulant and fibrinolytic factors in modulating the clinical severity of haemophilia patients. Brit J Haematol 2007; 138: 541–544.
Boylan B, Rice AS, Staercke C de, et al. Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations. J Thromb Haemost 2015; 13: 1036–1042.
Gupta M, Lillicrap D, Stain AM, et al. Therapeutic consequences for misdiagnosis of type 2N von Willebrand disease. Pediatr Blood Cancer 2011; 57: 1081–1083.
Mazurier C, Goudemand J, Hilbert L, et al. Type 2N von Willebrand disease: clinical manifestations, pathophysiology, laboratory diagnosis and molecular biology. Best Pract Res Clin Haematol 2001; 14: 337–347.
Pavlova A, Delev D, Pezeshkpoor B, et al. Haemophilia A mutations in patients with non-severe phenotype associated with a discrepancy between one-stage and chromogenic factor VIII activity assays. Thrombosis and haemostasis 2014; 111: 851–861.
Keeling DM, Sukhu K, Kemball-Cook G, et al. Diagnostic importance of the two-stage factor VIII:C assay demonstrated by a case of mild haemophilia associated with His1954-->Leu substitution in the factor VIII A3 domain. Br J Haematol 1999; 105: 1123–1126.
Published
2024-08-23
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Банчев А, Павлова А. Генетична диагностика при хемофилия А и В – приложение в клиничната практика. Редки болести и лекарства сираци [Internet]. 2024Aug.23 [cited 2024Nov.21];15(2):3-13. Available from: https://journal.raredis.org/index.php/RBLS/article/view/200
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Copyright (c) 2024 Атанас Банчев, Анна Павлова
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Съдържанието е достъпно под лиценза Creative Commons Attribution-NonCommercial 4.0 International License.
