Oculocutaneous albinism, Hermansky-Pudlak type 1 (HPS1) (oculocutaneous albinism, Hermansky-Pudlak syndrome) syndrome - Genes HPS1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S6, BLOC1S3 and AP3B1

The Hermansky-Pudlak syndrome (HPS: Hermansky-Pudlak syndrome) is an autosomal recessive genetic disease characterized by a oculocutaneous albinism (OCA), associated with a bleeding tendency due to absence of platelet granules and dysfunction lysosomal by accumulation of material ceroide in lysosomes. In addition, patients develop pulmonary involvement (pulmonary fibrosis) and granulomatous colitis. Affected patients usually die between 30 to 50 years for lung disease or bleeding.

They described nine different types of Hermansky-Pudlak, which can be distinguished by its signs and symptoms syndrome, as well as the underlying genetic causes. Types 1 and 4 are the most serious forms of the disease. Types 1, 2, and 4 are the only types associated with pulmonary fibrosis. Individuals with types 3, 5 and 6 have milder symptoms. Little is known about the signs, symptoms and severity of the types 7, 8 and 9.

They have been identified at least nine genes associated with Hermansky-Pudlak syndrome: HPS1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S6, BLOC1S3 and AP3B1. These genes encode proteins used to form four distinct protein complexes. These protein complexes play a role in shaping and traffic - related organelle lysosomes (LROS). LROS performs specialized functions and is found only in certain cell types, such as melanocytes, platelets and lung cells. Mutations in genes associated with Hermansky-Pudlak syndrome prevent the formation of LROS or impair functioning of these cellular structures. In general, mutations in genes involving the same complex proteins cause similar signs and symptoms. Individuals with this syndrome have oculocutaneous albinism because LROS within melanocytes can not produce and distribute melanin. Meanwhile, hemorrhages are caused by the absence of LROS inside platelets, which affects the ability of platelets to join and form a blood clot. Furthermore, mutations in some of the genes that cause Hermansky-Pudlak syndrome affect normal operation of LROS in lung cells, leading to pulmonary fibrosis.

Mutations in the gene HPS1, located on the long arm of chromosome 10 (10q23.1-q23.3) are responsible for about 75% of cases of Hermansky-Pudlak syndrome of in Puerto Rico. In other populations, about 45% of affected individuals have mutations in the gene HPS1. They have identified at least 31 HPS1 gene mutations in people with Hermansky-Pudlak syndrome type 1. Mutations in this gene, altering the size, structure and function LROS in cells throughout the body. The most frequent mutation causes a duplication of genetic material in gene HPS1. Specifically, this mutation results in an extra 16 nucleotides within the gene (1470_1486dup16).

Furthermore, mutations in the HPS3 gene, located on the long arm of chromosome 3 (3q24), are found in about 25% of persons suffering from Puerto Rico and about 20% of persons suffering from other areas . At least seven mutations in the gene are responsible HPS3 Hermansky-Pudlak syndrome type 3, a mild form of the disease. As mutations in the gene HPS1, mutations in the gene HPS3 alter the size, structure and function of LROS in cells throughout the body. A common mutation is a deletion of genetic material in gene HPS3. This deletion includes about 3900 nucleotides and is known as the 3.9 kb deletion (339_4260del3904). This mutation, found in affected individuals from the central region of Puerto Rico, inhibits protein coding any HPS3. Another mutation in the gene HPS3 has been found in people in Central and Eastern Jewish (Ashkenazi) Europe. This mutation, 1163 + 1G> A, results in the encoding of an abnormally short protein.

The other genes associated with Hermansky-Pudlak syndrome (HPS4, HPS5, HPS6, DTNBP1, BLOC1S6, BLOC1S3 and AP3B1) each represent a small percentage of cases of this disease.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform the detection of mutations associated with Hermansky-Pudlak syndrome, by complete PCR amplification of the exons of HPS1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S6, BLOC1S3 genes and AP3B1 respectively, and subsequent secuenciación.Se recommended to start the study by exons of the gene and the HPS3 HPS1 gene. If not, it is suggested further by sequencing other genes in order to optimize the best time / cost.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).