Genetics of hemophilia: Why mutations matter more than ever in diagnosis and treatment

As India grapples with the dual challenge of underdiagnosis and limited access to preventive care for hemophilia, understanding the genetic roots of the disorder has become increasingly crucial.

Firstpost talked to Dr Rahul Bhargava, Principal Director and Chief BMT, Fortis Memorial Research Institute, Gurugram, to shed light on how gene mutations influence the onset, transmission and treatment outlook of hemophilia.

Types of hemophilia

Two types of hemophilia exist: Hemophilia A and Hemophilia B. Hemophilia A is the result of F8 gene mutations, which encode clotting factor VIII. Hemophilia B occurs due to F9 gene mutations, which encode clotting factor IX.

Genetic location and prevalence

These genes are situated on the X chromosome, thus the disorder tends to be more prevalent in males. Because males possess only one X chromosome, a mutation in this single copy is sufficient to create the disorder. Females, possessing two X chromosomes, are typically carriers; they can be asymptomatic but can transmit the defective gene to their children.

Diversity of mutations

The mutations in the genes can be quite diverse. They include point mutations, where one DNA base is altered, and deletions, insertions, or inversions of longer segments. The inversion of intron 22 within the F8 gene, known to account for almost half of all cases of severe Hemophilia A, is a highly famous example.

Impact on clotting proteins

These mutations interfere with the regular production or action of blood-clotting proteins, such that there’s lowered or none present in the circulating blood. Based on the proportion of a clotting protein that is deficient or dysfunctional, the severity of hemophilia varies—it can be either mild, moderate, or severe.

Inheritance patterns

Inherited gene mutations are most often transmitted from carrier mother to son. But in approximately 30% of instances, the mutations occur spontaneously, with no family history. This is the result of random mistakes in DNA replication or cell division.

Importance of genetic screening

These sporadic mutations are as significant and point out the value of genetic screening and counseling, even if hemophilia has never been diagnosed within a family. Genetic testing is an important tool in determining the exact mutation that causes hemophilia in a person. Not only does this assist in proper diagnosis and treatment planning, but it also helps in making informed choices regarding future pregnancies for families.

Advances in gene therapy

Gene therapy, with its recent advances, brings new hope by attempting to repair the faulty gene or add a working copy to replace clotting factor levels. Finally, gene mutations are the major reason why hemophilia occurs, playing a huge role in determining the severity and heredity of the disease. Knowledge of the genetic factors is essential for effectively managing the condition as well as creating possible long-term cures.