<abstract xmlns="http://www.w3.org/1999/xhtml">Haemophilia is an X-linked inherited disorder that affects males and females, though the bleeding risk in girls and women has traditionally been under-recognised. About one third of haemophilia cases occur in individuals where there is no known family history. The gene mutations for rare bleeding disorders are not carried on the X chromosome and are therefore not sex-linked; however, the risk of passing on the condition is greatly increased for consanguineous parents where both parents may carry a copy of the fault in the genetic code which causes the condition. Genetic testing should be offered to every prospective mother, ideally before conception. This should be supported by counselling as the implications for family planning are profound.Von Willebrand factor (VWF) has an important role in primary and secondary haemostasis. Loss of function or low levels of VWF are associated with spontaneous bleeding causing nosebleeds, heavy periods and bruising as well as jpost-surgical bleeding. Joint bleeding and intracranial haemorrhage can also occur in those with a severe type of VWF. Diagnosis depends on bleeding assessment, family history and measurement of VWF. There are three types of VWD: Types 1 and 3 are caused by low or absent levels of VWD; Type 2 is caused by loss of function. Of these, Type 3 VWD is associated with the most severe bleeding risk but there is wide variation in bleeding phenotype among the other sub-types. The correlation between genetic mutation and bleeding phenotype is weak in VWD; therefore genetic testing is mainly useful for interpreting the risk when planning a family and to allow prenatal diagnosis in severe bleeding disorders.Genetic testing is essential for prospective parents to make fully informed decisions about having a family and how or whether to proceed with a pregnancy. The rationale for prenatal testing is to determine the bleeding status of the foetus and to inform decisions about managing delivery. Women may choose to terminate a pregnancy to avoid having a child with severe haemophilia. For some couples the option of adoption or not having children may be explored. Options for prenatal diagnostic testing include non-invasive methods, e.g. assessment of free foetal DNA in maternal plasma to determine the sex of a baby from 10 weeks in pregnancy, and invasive methods, e.g. chorionic villus sampling or amniocentesis, to determine the inheritance of the genetic mutation. Invasive methods are associated with a very small increased risk of pregnancy loss or early labour, which many couples feel is an unacceptable risk. Advanced techniques such as preimplantation screening also available, but require a huge commitment as this involves an IVF technique.</abstract>

Haemophilia is an X-linked inherited disorder that affects males and females, though the bleeding risk in girls and women has traditionally been under-recognised. About one third of haemophilia cases occur in individuals where there is no known family history. The gene mutations for rare bleeding disorders are not carried on the X chromosome and are therefore not sex-linked; however, the risk of passing on the condition is greatly increased for consanguineous parents where both parents may carry a copy of the fault in the genetic code which causes the condition. Genetic testing should be offered to every prospective mother, ideally before conception. This should be supported by counselling as the implications for family planning are profound.Von Willebrand factor (VWF) has an important role in primary and secondary haemostasis. Loss of function or low levels of VWF are associated with spontaneous bleeding causing nosebleeds, heavy periods and bruising as well as jpost-surgical bleeding. Joint bleeding and intracranial haemorrhage can also occur in those with a severe type of VWF. Diagnosis depends on bleeding assessment, family history and measurement of VWF. There are three types of VWD: Types 1 and 3 are caused by low or absent levels of VWD; Type 2 is caused by loss of function. Of these, Type 3 VWD is associated with the most severe bleeding risk but there is wide variation in bleeding phenotype among the other sub-types. The correlation between genetic mutation and bleeding phenotype is weak in VWD; therefore genetic testing is mainly useful for interpreting the risk when planning a family and to allow prenatal diagnosis in severe bleeding disorders.Genetic testing is essential for prospective parents to make fully informed decisions about having a family and how or whether to proceed with a pregnancy. The rationale for prenatal testing is to determine the bleeding status of the foetus and to inform decisions about managing delivery. Women may choose to terminate a pregnancy to avoid having a child with severe haemophilia. For some couples the option of adoption or not having children may be explored. Options for prenatal diagnostic testing include non-invasive methods, e.g. assessment of free foetal DNA in maternal plasma to determine the sex of a baby from 10 weeks in pregnancy, and invasive methods, e.g. chorionic villus sampling or amniocentesis, to determine the inheritance of the genetic mutation. Invasive methods are associated with a very small increased risk of pregnancy loss or early labour, which many couples feel is an unacceptable risk. Advanced techniques such as preimplantation screening also available, but require a huge commitment as this involves an IVF technique.

Genetics 101: understanding transmission and genetic testing of inherited bleeding disorders

The Journal of Haemophilia Practice

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Haemophilia is an X-linked inherited disorder that affects males and females, though the bleeding risk in girls and women has traditionally been...

THE MAN SAW THE DOG HIT THE CAN	Normal DNA
THE MAN SAW THE DOT HIT THE CAN	Missense	A change in one DNA base pair resulting in substitution of one amino acid for another in the protein made by the gene
THE MAN SAW THE DOG *	Nonsense	A change in one DNA base pair that prematurely signals the cell to stop building a protein, resulting in a shortened protein
THE MAN SAW THE DOG * THE CAN	Deletion	Removes a piece of DNA
THE MAN SAW THE FAT DOG HIT THE CAN	Insertion	Changes the number of DNA bases in a gene by adding a piece of DNA
THE MAN SAW THE *OGH ITT HEC AN	Frameshift	Occurs when the addition or loss of DNA bases changes a gene’s reading frame. The groups of three bases that code a single amino acid are shifted, thereby changing the code

Genetics 101: understanding transmission and genetic testing of inherited bleeding disorders

Article Category: Women With Bleeding Disorders

Online veröffentlicht: 21. Okt. 2019

Seitenbereich: 10 - 17

DOI: https://doi.org/10.17225/jhp00139

Schlüsselwörter
Women with bleeding disorders, haemophilia, von Willebrand disease, transmission, inheritance, diagnosis, prenatal testing

© 2019 Eugenia Biguzzi, Karin van Galen, Rezan A Kadir, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1

Figure 2

Figure 3

Types of DNA mutationThe changes in the letters/words in the left hand column demonstrate the type, mechanism and results of DNA mutation. Every letter of the words that make up the sentence represents a DNA base. Three consecutive letters codify an amino acid of the protein.

Genetics 101: understanding transmission and genetic testing of inherited bleeding disorders

Article Category: Women With Bleeding Disorders

Online veröffentlicht: 21. Okt. 2019

Seitenbereich: 10 - 17

DOI: https://doi.org/10.17225/jhp00139

SchlüsselwörterWomen with bleeding disorders, haemophilia, von Willebrand disease, transmission, inheritance, diagnosis, prenatal testing

© 2019 Eugenia Biguzzi, Karin van Galen, Rezan A Kadir, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1

Figure 2

Figure 3

Types of DNA mutationThe changes in the letters/words in the left hand column demonstrate the type, mechanism and results of DNA mutation. Every letter of the words that make up the sentence represents a DNA base. Three consecutive letters codify an amino acid of the protein.

Schlüsselwörter
Women with bleeding disorders, haemophilia, von Willebrand disease, transmission, inheritance, diagnosis, prenatal testing