Genetic diagnosis of haemophilia and other inherited bleeding disorders

Flora Peyvandi, G. Jayandharan, M. Chandy, A. Srivastava, S. M. Nakaya, M. J. Johnson, A. R. Thompson, A. Goodeve, I. Garagiola, S. Lavoretano, M. Menegatti, R. Palla, M. Spreafico, L. Tagliabue, R. Asselta, S. Duga, P. M. Mannucci

Research output: Contribution to journalArticle

Abstract

Inherited deficiencies of plasma proteins involved in blood coagulation generally lead to lifelong bleeding disorders, whose severity is inversely proportional to the degree of factor deficiency. Haemophilia A and B, inherited as X-linked recessive traits, are the most common hereditary hemorrhagic disorders caused by a deficiency or dysfunction of blood coagulation factor VIII (FVIII) and factor IX (FIX). Together with von Willebrand's disease, a defect of primary haemostasis, these X-linked disorders include 95% to 97% of all the inherited deficiencies of coagulation factors. The remaining defects, generally transmitted as autosomal recessive traits, are rare with prevalence of the presumably homozygous forms in the general population of 1:500.000 for FVII deficiency and 1 in 2 million for prothrombin (FII) and factor XIII (FXIII) deficiency. Molecular characterization, carrier detection and prenatal diagnosis remain the key steps for the prevention of the birth of children affected by coagulation disorders in developing countries, where patients with these deficiencies rarely live beyond childhood and where management is still largely inadequate. These characterizations are possible by direct or indirect genetic analysis of genes involved in these diseases, and the choice of the strategy depends on the effective available budget and facilities to achieve a large benefit. In countries with more advanced molecular facilities and higher budget resources, the most appropriate choice in general is a direct strategy for mutation detection. However, in countries with limited facilities and low resources, carrier detection and prenatal diagnosis are usually performed by linkage analysis with genetic markers. This article reviews the genetic diagnosis of haemophilia, genetics and inhibitor development, genetics of von Willebrand's disease and of rare bleeding disorders.

Original languageEnglish
Pages (from-to)82-89
Number of pages8
JournalHaemophilia
Volume12
Issue numberSUPPL. 3
DOIs
Publication statusPublished - Jul 2006

Fingerprint

von Willebrand Diseases
Hemophilia A
Budgets
Prenatal Diagnosis
Factor XIII Deficiency
Hemorrhage
Hemorrhagic Disorders
Hemophilia B
X-Linked Genes
Factor IX
Blood Coagulation Factors
Factor VIII
Prothrombin
Blood Coagulation
Hemostasis
Genetic Markers
Developing Countries
Blood Proteins
Parturition
Mutation

Keywords

  • Carrier detection and prenatal diagnosis
  • Genetic diagnosis
  • Haemophilia A and B
  • Inhibitor development
  • Rare bleeding disorders
  • Von Willebrand's disease

ASJC Scopus subject areas

  • Hematology

Cite this

Peyvandi, F., Jayandharan, G., Chandy, M., Srivastava, A., Nakaya, S. M., Johnson, M. J., ... Mannucci, P. M. (2006). Genetic diagnosis of haemophilia and other inherited bleeding disorders. Haemophilia, 12(SUPPL. 3), 82-89. https://doi.org/10.1111/j.1365-2516.2006.01263.x

Genetic diagnosis of haemophilia and other inherited bleeding disorders. / Peyvandi, Flora; Jayandharan, G.; Chandy, M.; Srivastava, A.; Nakaya, S. M.; Johnson, M. J.; Thompson, A. R.; Goodeve, A.; Garagiola, I.; Lavoretano, S.; Menegatti, M.; Palla, R.; Spreafico, M.; Tagliabue, L.; Asselta, R.; Duga, S.; Mannucci, P. M.

In: Haemophilia, Vol. 12, No. SUPPL. 3, 07.2006, p. 82-89.

Research output: Contribution to journalArticle

Peyvandi, F, Jayandharan, G, Chandy, M, Srivastava, A, Nakaya, SM, Johnson, MJ, Thompson, AR, Goodeve, A, Garagiola, I, Lavoretano, S, Menegatti, M, Palla, R, Spreafico, M, Tagliabue, L, Asselta, R, Duga, S & Mannucci, PM 2006, 'Genetic diagnosis of haemophilia and other inherited bleeding disorders', Haemophilia, vol. 12, no. SUPPL. 3, pp. 82-89. https://doi.org/10.1111/j.1365-2516.2006.01263.x
Peyvandi F, Jayandharan G, Chandy M, Srivastava A, Nakaya SM, Johnson MJ et al. Genetic diagnosis of haemophilia and other inherited bleeding disorders. Haemophilia. 2006 Jul;12(SUPPL. 3):82-89. https://doi.org/10.1111/j.1365-2516.2006.01263.x
Peyvandi, Flora ; Jayandharan, G. ; Chandy, M. ; Srivastava, A. ; Nakaya, S. M. ; Johnson, M. J. ; Thompson, A. R. ; Goodeve, A. ; Garagiola, I. ; Lavoretano, S. ; Menegatti, M. ; Palla, R. ; Spreafico, M. ; Tagliabue, L. ; Asselta, R. ; Duga, S. ; Mannucci, P. M. / Genetic diagnosis of haemophilia and other inherited bleeding disorders. In: Haemophilia. 2006 ; Vol. 12, No. SUPPL. 3. pp. 82-89.
@article{f64fb079b80e4483a95de899df7a7de8,
title = "Genetic diagnosis of haemophilia and other inherited bleeding disorders",
abstract = "Inherited deficiencies of plasma proteins involved in blood coagulation generally lead to lifelong bleeding disorders, whose severity is inversely proportional to the degree of factor deficiency. Haemophilia A and B, inherited as X-linked recessive traits, are the most common hereditary hemorrhagic disorders caused by a deficiency or dysfunction of blood coagulation factor VIII (FVIII) and factor IX (FIX). Together with von Willebrand's disease, a defect of primary haemostasis, these X-linked disorders include 95{\%} to 97{\%} of all the inherited deficiencies of coagulation factors. The remaining defects, generally transmitted as autosomal recessive traits, are rare with prevalence of the presumably homozygous forms in the general population of 1:500.000 for FVII deficiency and 1 in 2 million for prothrombin (FII) and factor XIII (FXIII) deficiency. Molecular characterization, carrier detection and prenatal diagnosis remain the key steps for the prevention of the birth of children affected by coagulation disorders in developing countries, where patients with these deficiencies rarely live beyond childhood and where management is still largely inadequate. These characterizations are possible by direct or indirect genetic analysis of genes involved in these diseases, and the choice of the strategy depends on the effective available budget and facilities to achieve a large benefit. In countries with more advanced molecular facilities and higher budget resources, the most appropriate choice in general is a direct strategy for mutation detection. However, in countries with limited facilities and low resources, carrier detection and prenatal diagnosis are usually performed by linkage analysis with genetic markers. This article reviews the genetic diagnosis of haemophilia, genetics and inhibitor development, genetics of von Willebrand's disease and of rare bleeding disorders.",
keywords = "Carrier detection and prenatal diagnosis, Genetic diagnosis, Haemophilia A and B, Inhibitor development, Rare bleeding disorders, Von Willebrand's disease",
author = "Flora Peyvandi and G. Jayandharan and M. Chandy and A. Srivastava and Nakaya, {S. M.} and Johnson, {M. J.} and Thompson, {A. R.} and A. Goodeve and I. Garagiola and S. Lavoretano and M. Menegatti and R. Palla and M. Spreafico and L. Tagliabue and R. Asselta and S. Duga and Mannucci, {P. M.}",
year = "2006",
month = "7",
doi = "10.1111/j.1365-2516.2006.01263.x",
language = "English",
volume = "12",
pages = "82--89",
journal = "Haemophilia",
issn = "1351-8216",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "SUPPL. 3",

}

TY - JOUR

T1 - Genetic diagnosis of haemophilia and other inherited bleeding disorders

AU - Peyvandi, Flora

AU - Jayandharan, G.

AU - Chandy, M.

AU - Srivastava, A.

AU - Nakaya, S. M.

AU - Johnson, M. J.

AU - Thompson, A. R.

AU - Goodeve, A.

AU - Garagiola, I.

AU - Lavoretano, S.

AU - Menegatti, M.

AU - Palla, R.

AU - Spreafico, M.

AU - Tagliabue, L.

AU - Asselta, R.

AU - Duga, S.

AU - Mannucci, P. M.

PY - 2006/7

Y1 - 2006/7

N2 - Inherited deficiencies of plasma proteins involved in blood coagulation generally lead to lifelong bleeding disorders, whose severity is inversely proportional to the degree of factor deficiency. Haemophilia A and B, inherited as X-linked recessive traits, are the most common hereditary hemorrhagic disorders caused by a deficiency or dysfunction of blood coagulation factor VIII (FVIII) and factor IX (FIX). Together with von Willebrand's disease, a defect of primary haemostasis, these X-linked disorders include 95% to 97% of all the inherited deficiencies of coagulation factors. The remaining defects, generally transmitted as autosomal recessive traits, are rare with prevalence of the presumably homozygous forms in the general population of 1:500.000 for FVII deficiency and 1 in 2 million for prothrombin (FII) and factor XIII (FXIII) deficiency. Molecular characterization, carrier detection and prenatal diagnosis remain the key steps for the prevention of the birth of children affected by coagulation disorders in developing countries, where patients with these deficiencies rarely live beyond childhood and where management is still largely inadequate. These characterizations are possible by direct or indirect genetic analysis of genes involved in these diseases, and the choice of the strategy depends on the effective available budget and facilities to achieve a large benefit. In countries with more advanced molecular facilities and higher budget resources, the most appropriate choice in general is a direct strategy for mutation detection. However, in countries with limited facilities and low resources, carrier detection and prenatal diagnosis are usually performed by linkage analysis with genetic markers. This article reviews the genetic diagnosis of haemophilia, genetics and inhibitor development, genetics of von Willebrand's disease and of rare bleeding disorders.

AB - Inherited deficiencies of plasma proteins involved in blood coagulation generally lead to lifelong bleeding disorders, whose severity is inversely proportional to the degree of factor deficiency. Haemophilia A and B, inherited as X-linked recessive traits, are the most common hereditary hemorrhagic disorders caused by a deficiency or dysfunction of blood coagulation factor VIII (FVIII) and factor IX (FIX). Together with von Willebrand's disease, a defect of primary haemostasis, these X-linked disorders include 95% to 97% of all the inherited deficiencies of coagulation factors. The remaining defects, generally transmitted as autosomal recessive traits, are rare with prevalence of the presumably homozygous forms in the general population of 1:500.000 for FVII deficiency and 1 in 2 million for prothrombin (FII) and factor XIII (FXIII) deficiency. Molecular characterization, carrier detection and prenatal diagnosis remain the key steps for the prevention of the birth of children affected by coagulation disorders in developing countries, where patients with these deficiencies rarely live beyond childhood and where management is still largely inadequate. These characterizations are possible by direct or indirect genetic analysis of genes involved in these diseases, and the choice of the strategy depends on the effective available budget and facilities to achieve a large benefit. In countries with more advanced molecular facilities and higher budget resources, the most appropriate choice in general is a direct strategy for mutation detection. However, in countries with limited facilities and low resources, carrier detection and prenatal diagnosis are usually performed by linkage analysis with genetic markers. This article reviews the genetic diagnosis of haemophilia, genetics and inhibitor development, genetics of von Willebrand's disease and of rare bleeding disorders.

KW - Carrier detection and prenatal diagnosis

KW - Genetic diagnosis

KW - Haemophilia A and B

KW - Inhibitor development

KW - Rare bleeding disorders

KW - Von Willebrand's disease

UR - http://www.scopus.com/inward/record.url?scp=33646138963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646138963&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2516.2006.01263.x

DO - 10.1111/j.1365-2516.2006.01263.x

M3 - Article

C2 - 16684001

AN - SCOPUS:33646138963

VL - 12

SP - 82

EP - 89

JO - Haemophilia

JF - Haemophilia

SN - 1351-8216

IS - SUPPL. 3

ER -