Genetics of Hermansky-Pudlak Syndrome

HPS is a rare genetic disorder, and is inherited autosomal recessively. Although found in many countries, it is most commonly found in the northwest and central regions of Puerto Rico. There is currently no cure for HPS, and so only the symptoms and associated complications can be treated.

There are several types of HPS, and both symptoms and severity vary from one person to another. Generally, symptoms can be split into three groups:

• Albinism (tyrosinase-positive form) – varied pigmentation in hair, eyes and skin, and other vision problems.
• Bleeding problems – resulting from abnormal blood platelets. These platelets are involved in clotting, and the defect can result in prolonged bleeding.
• Cell storage issues – build-up of a substance called ceriod. This can cause problems in several organs, such as pulmonary fibrosis, kidney disease and inflammatory bowel disease.

Autosomal recessive inheritance refers to disorders where the mutated gene is inherited from both parents. The term “autosomal” refers to the autosomal chromosomes, which mean all non-sex chromosomes (pairs 1-22). In HPS, several genes are known to be relevant, and these are located on chromosome 10.

When a trait is recessive, it will only be expressed in someone with two mutated versions of the gene. This is how HPS is inherited. If someone has one mutated version and one normal version, they will be a carrier. Carriers do not have the disease, but may pass on the mutated gene to their children.

How does HPS inheritance work? If both parents have the mutated gene, any children they have will have:

• A 25% chance of having HPS.
• A 50% chance of being a carrier of HPS.
• A 25% chance of not having or being a carrier of HPS.

In his Hermansky-Pudlak Syndrome article on the Gene Reviews website, author Dr William Gahl lists the following genes that play a role in HPS: “HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, and BLOC1S3”. Other genes are thought to be involved, and hopefully future research will identify them.

This rare genetic disorder is usually diagnosed by recording symptoms and special testing of blood platelets. Certain genes can be tested, which is usually carried out if there is a family history, but this is limited due to the involvement of other unknown genes. Prenatal testing is possible, but not widely available. Genetic counselors can offer advice about available testing.

National Society of Genetic Counselors

Hermansky-Pudlak Syndrome Network

• Hermansky-Pudlak Syndrome, Gene Reviews website, updated: 27^th November 2007, author: Dr William A Gahl.
• Hermansky-Pudlak Syndrome, eMedicine website, updated: Feb 20th 2008, accessed: 8th June 2009, authors: Natalio. J Izquierdo and William Townsend.
• What is HPS?, Hermansky-Pudlak Syndrome Network Inc website, accessed: 8th June 2009, no author specified.