Decoding the Bombay Phenotype: Understanding, Diagnosing, and Genetic Testing

Expert Reviewed By: ⁠Dr. Brandon Colby MD

The Bombay phenotype, a rare blood group variant, has intrigued researchers and clinicians since its discovery in the 1950s. This blood group, characterized by the absence of H antigen on red blood cells, can lead to challenges in blood transfusion and organ transplantation. In this article, we will explore the genetic basis of the Bombay phenotype, the methods available for diagnosis, and the role of genetic testing in managing this rare blood group.

Understanding the Bombay Phenotype

The ABO blood group system, discovered by Karl Landsteiner in 1901, is based on the presence or absence of A, B, and H antigens on the surface of red blood cells. The Bombay phenotype, first identified in Bombay (now Mumbai), India, is characterized by the absence of the H antigen, which is the precursor for the A and B antigens. This absence is caused by the inheritance of two recessive genes that control H antigen formation in erythrocytes1.

Individuals with the Bombay phenotype can only receive blood from other Bombay phenotype donors, making it challenging to find compatible blood for transfusion. Moreover, the rarity of this blood group, which occurs in approximately 1 in 10,000 individuals in India and 1 in a million in Europe, makes it even more difficult to find suitable donors.

Diagnosing the Bombay Phenotype

Diagnosing the Bombay phenotype typically involves a combination of serological methods and molecular genetic analysis. Serological testing, which examines the presence or absence of antigens and antibodies in the blood, can identify the absence of H antigen and the presence of anti-H antibodies, which are characteristic of the Bombay phenotype.

Molecular genetic analysis can provide further confirmation of the diagnosis by identifying specific genetic mutations responsible for the Bombay phenotype. Several studies have identified novel nonfunctional FUT1 alleles in individuals with the Bombay phenotype23. These mutations result in the loss of function of the fucosyltransferase enzyme, which is responsible for the synthesis of the H antigen.

Genetic Testing for the Bombay Phenotype

Confirming the Diagnosis

Genetic testing can be a valuable tool in confirming the diagnosis of the Bombay phenotype, especially in cases where serological testing is inconclusive. By identifying the specific FUT1 mutations responsible for the absence of H antigen, clinicians can be more confident in their diagnosis and make better-informed decisions about blood transfusion choices4.

Carrier Detection and Family Screening

Genetic testing can also be used to identify carriers of FUT1 mutations in families with a history of the Bombay phenotype. By determining the carrier status of family members, clinicians can provide genetic counseling and guidance on family planning. Additionally, screening family members for the Bombay phenotype can help identify potential blood donors for individuals with this rare blood group.

Prenatal and Preimplantation Genetic Diagnosis

For couples at risk of having a child with the Bombay phenotype, prenatal genetic testing can be performed to determine the fetus’s blood group status. This information can help clinicians prepare for potential blood transfusion needs during delivery. Alternatively, preimplantation genetic diagnosis (PGD) can be performed during in vitro fertilization (IVF) to select embryos without the Bombay phenotype for implantation, reducing the risk of having a child with this rare blood group.

Conclusion

The Bombay phenotype is a rare blood group variant with significant implications for blood transfusion and organ transplantation. Understanding the genetic basis of this blood group and employing genetic testing in diagnosis, carrier detection, and prenatal screening can help clinicians manage this condition more effectively and improve patient outcomes. As our knowledge of the molecular mechanisms underlying the Bombay phenotype continues to expand, so too will our ability to provide better care for individuals with this rare blood group.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)