Hermansky-Pudlak Syndrome NGS panel
|AP3B1, AP3D1, BLOC1S3, BLOC1S5, BLOC1S6, DTNBP1, HPS1, HPS3, HPS4, HPS5, HPS6
List of diseases covered by the panel
||NGS panel with CNV analysis
||2-4 ml of blood with anticoagulant EDTA
1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of Hermansky-Pudlak syndrome types
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling
Hermansky-Pudlak syndrome (HPS) is a group of rare hereditary disorders characterized by defective biogenesis of lysosome-related organelles. Clinical manifestations include oculocutaneous albinism, bleeding diathesis, and in some individuals pulmonary fibrosis, granulomatous colitis, immunodeficiency, or abnormal storage of fatty-like substance (ceroid lipofuscin) in various tissues of the body.
There are eleven different types of HPS, which can be stratified by their signs and symptoms and underlying genetic cause. Types 1 and 4 are the most severe forms of the disorder. Types 1, 2, and 4 are the only types associated with pulmonary fibrosis. Individuals with type 3, 5, or 6 have the mildest symptoms. Very few is known about the signs, symptoms, and severity of types 7, 8, 9, 10 and 11.
The test covers the known genetic causes of HPS. The disease is inherited in an autosomal recessive pattern.
HPS is a rare disorder in most populations and is estimated to affect 1: 500 000 to 1 000 000 individuals worldwide. Type 1 is more common in northwest Puerto Rico where about 1: 1800 people are affected. Type 3 is common in people from central Puerto Rico. Groups of affected individuals have been identified in many other regions, including India, Japan, the United Kingdom, and Western Europe. HPS is the third most prevalent form of albinism.
Huizing M, Malicdan MCV, Gochuico BR, et al. Hermansky-Pudlak Syndrome. 2000 Jul 24 [Updated 2017 Oct 26]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. https://www.ncbi.nlm.nih.gov/books/NBK1287/. PMID:20301464
Huizing M, Malicdan MCV, Wang JA, et al. Hermansky-Pudlak syndrome: Mutation update. Hum Mutat. 2020;41(3):543-580. doi:10.1002/humu.23968. PMID:31898847
Merideth MA, Introne WJ, Wang JA, O’Brien KJ, Huizing M, Gochuico BR. Genetic variants associated with Hermansky-Pudlak syndrome. Platelets. 2020;31(4):544-547. doi:10.1080/09537104.2019.1663810. PMID:32436471
Pennamen P, Le L, Tingaud-Sequeira A, et al. BLOC1S5 pathogenic variants cause a new type of Hermansky-Pudlak syndrome [published online ahead of print, 2020 Jun 22]. Genet Med. 2020;10.1038/s41436-020-0867-5. doi:10.1038/s41436-020-0867-5. PMID:32565547