Bernard-Soulier syndrome is a bleeding disorder associated with abnormal platelets, which are blood cells involved in blood clotting. In affected individuals, platelets are unusually large and fewer in number than usual (a combination known as macrothrombocytopenia). People with Bernard-Soulier syndrome tend to bruise easily and have an increased risk of nosebleeds (epistaxis). They may also experience abnormally heavy or prolonged bleeding following minor injury or surgery or even without trauma (spontaneous bleeding). Rarely, bleeding under the skin causes tiny red or purple spots on the skin called petechiae. Women with Bernard-Soulier syndrome often have heavy or prolonged menstrual bleeding (menorrhagia).

Bernard-Soulier syndrome is caused by mutations in one of three genes: GP1BA, GP1BB, or GP9. The proteins produced from these genes are pieces (subunits) of a protein complex called glycoprotein (GP)Ib-IX-V. This complex is found on the surface of platelets and plays an important role in blood clotting.

The GPIb-IX-V complex can attach (bind) to a protein called von Willebrand factor, fitting together like a lock and its key. Von Willebrand factor is found on the inside surface of blood vessels, particularly when there is an injury. Binding of the GPIb-IX-V complex to von Willebrand factor allows platelets to stick to the blood vessel wall at the site of the injury. These platelets form clots, plugging holes in the blood vessels to help stop bleeding.

Most mutations in GP1BA, GP1BB, or GP9 prevent the formation of the GPIb-IX-V complex on the surface of platelets. Other mutations impair the complex's interaction with von Willebrand factor. All of these mutations impair clot formation, which leads to the excessive bleeding characteristic of Bernard-Soulier syndrome.

Normal Function

The GP1BA gene provides instructions for making a protein called glycoprotein Ib-alpha (GPIbα). This protein is one piece (subunit) of a protein complex called GPIb-IX-V, which plays a role in blood clotting. GPIb-IX-V is found on the surface of small cells called platelets, which circulate in blood and are an essential component of blood clots. The complex can attach (bind) to a protein called von Willebrand factor, fitting together like a lock and its key. Von Willebrand factor is found on the inside surface of blood vessels, particularly when there is an injury. Binding of the GPIb-IX-V complex to von Willebrand factor allows platelets to stick to the blood vessel wall at the site of the injury. These platelets form clots, plugging holes in the blood vessels to help stop bleeding.

To form the GPIb-IX-V complex, GPIbα interacts with other protein subunits called GPIb-beta, GPIX, and GPV, each of which is produced from a different gene. GPIbα is essential for assembly of the complex at the platelet surface. It is the piece of the complex that interacts with von Willebrand factor to trigger blood clotting. GPIbα also interacts with other blood clotting proteins to aid in other steps of the clotting process.

Health Conditions Related to Genetic Changes

Bernard-Soulier syndrome

At least 54 GP1BA gene mutations have been found to cause Bernard-Soulier syndrome, a condition characterized by a reduced number of platelets that are larger than normal (macrothrombocytopenia) and excessive bleeding. Some of these mutations lead to production of an altered GPIbα subunit that is likely broken down too soon or that cannot get to the platelet surface. Lack of this subunit on the surface of platelets prevents formation of the GPIb-IX-V complex. Without GPIb-IX-V, platelets cannot come together at the site of an injury to form a clot, leading to the bleeding problems associated with Bernard-Soulier syndrome. Other mutations lead to production of a subunit that can form GPIb-IX-V complexes but cannot interact with von Willebrand factor, which also impairs the accumulation of platelets necessary for clotting.

Other disorders

At least six mutations in the GP1BA gene can cause another bleeding disorder called platelet-type von Willebrand disease (also known as pseudo-von Willebrand disease). This disorder is characterized by a reduced number of platelets in the blood (thrombocytopenia) and mild bleeding abnormalities. In contrast to mutations that cause Bernard-Soulier syndrome (described above), mutations involved in platelet-type von Willebrand disease lead to excessive binding of the GPIb-IX-V complex to von Willebrand factor. Because platelets containing the altered complex attach to von Willebrand factor without an injury to the blood vessel, fewer platelets are available for clot formation when an injury occurs, which leads to excessive bleeding in people with platelet-type von Willebrand disease.

Other Names for This Gene

• antigen CD42b-alpha
• BDPLT1
• BDPLT3
• BSS
• CD42B
• CD42b-alpha
• DBPLT3
• glycoprotein Ib (platelet), alpha polypeptide
• glycoprotein Ib platelet alpha subunit
• GP-Ib alpha
• GP1B
• GPIbA
• GPIbalpha
• platelet glycoprotein Ib alpha chain precursor
• platelet membrane glycoprotein 1b-alpha subunit
• VWDP

Genomic Location

Normal Function

The GP1BB gene provides instructions for making a protein called glycoprotein 1b-beta (GPIbβ). This protein is one piece (subunit) of a protein complex called GPIb-IX-V, which plays a role in blood clotting. GPIb-IX-V is found on the surface of small cells called platelets, which circulate in blood and are an essential component of blood clots. The complex can attach (bind) to a protein called von Willebrand factor, fitting together like a lock and its key. Von Willebrand factor is found on the inside surface of blood vessels, particularly when there is an injury. Binding of the GPIb-IX-V complex to von Willebrand factor allows platelets to stick to the blood vessel wall at the site of the injury. These platelets form clots, plugging holes in the blood vessels to help stop bleeding.

To form the GPIb-IX-V complex, GPIbβ interacts with other protein subunits called GPIb-alpha, GPIX, and GPV, each of which is produced from a different gene. GPIbβ is essential for assembly of the complex at the platelet surface and helps stabilize the complex once it is formed.

Health Conditions Related to Genetic Changes

Bernard-Soulier syndrome

At least 32 GP1BB gene mutations have been found to cause Bernard-Soulier syndrome, a condition characterized by a reduced number of platelets that are larger than normal (macrothrombocytopenia) and excessive bleeding. These mutations lead to production of an altered GPIbβ subunit that is likely broken down too soon or that cannot get to the platelet surface. Lack of this subunit on the surface of platelets prevents formation of the GPIb-IX-V complex. Without GPIb-IX-V, platelets cannot come together at the site of an injury to form a clot, leading to the bleeding problems associated with Bernard-Soulier syndrome.

Other Names for This Gene

• antigen CD42b-beta
• BDPLT1
• BS
• CD42C
• glycoprotein Ib (platelet), beta polypeptide
• glycoprotein Ib platelet beta subunit
• GP-Ib beta
• GPIBB
• GPIbbeta
• nuclear localization signal deleted in velocardiofacial syndrome
• platelet glycoprotein Ib beta chain precursor
• platelet membrane glycoprotein Ib beta
• truncated platelet membrane glycoprotein Ib beta

Genomic Location

Normal Function

The GP9 gene provides instructions for making a protein called glycoprotein IX (GPIX). This protein is one piece (subunit) of a protein complex called GPIb-IX-V, which plays a role in blood clotting. GPIb-IX-V is found on the surface of small cells called platelets, which circulate in blood and are an essential component of blood clots. The complex can attach (bind) to a protein called von Willebrand factor, fitting together like a lock and its key. Von Willebrand factor is found on the inside surface of blood vessels, particularly when there is an injury. Binding of the GPIb-IX-V complex to von Willebrand factor allows platelets to stick to the blood vessel wall at the site of the injury. These platelets form clots, plugging holes in the blood vessels to help stop bleeding.

To form the GPIb-IX-V complex, GPIX interacts with other protein subunits called GPIb-alpha, GPIb-beta, and GPV, each of which is produced from a different gene. GPIX is essential for assembly of the complex at the platelet surface and helps stabilize the complex once it is formed.

Health Conditions Related to Genetic Changes

Bernard-Soulier syndrome

At least 28 GP9 gene mutations have been found to cause Bernard-Soulier syndrome, a condition characterized by a reduced number of platelets that are larger than normal (macrothrombocytopenia) and excessive bleeding. These mutations lead to production of an altered GPIX subunit that is likely broken down too soon or that cannot get to the platelet surface. Lack of this subunit on the surface of platelets prevents formation of the GPIb-IX-V complex. Without GPIb-IX-V, platelets cannot come together at the site of an injury to form a clot, leading to the bleeding problems associated with Bernard-Soulier syndrome.

Other Names for This Gene

• CD42a
• glycoprotein 9
• glycoprotein IX (platelet)
• GPIX
• platelet glycoprotein IX precursor

Genomic Location

Most cases of Bernard-Soulier syndrome are inherited in an autosomal recessive pattern, which means both copies of the GP1BA, GP1BB, or GP9 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene. Although most people with only one copy of the mutated gene do not show signs and symptoms of the condition, some have platelets that are slightly larger than normal or very mild bleeding abnormalities.

Rare cases of Bernard-Soulier syndrome caused by mutations in the GP1BA or GP1BB gene are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. These individuals inherit the condition from an affected parent.

Bernard-Soulier syndrome is estimated to occur in 1 in 1 million individuals; however, some doctors think the condition is underdiagnosed and may be more common.