Hermansky-Pudlak Syndrome: HPS4 Gene Deletion/Duplication

Condition Description

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive, multisystemic disorder.  The main clinical features of HPS include oculocutaneous albinism which presents as hypopigmentation of the skin and hair; reduced iris and retinal pigments; foveal hypoplasia; nystagmus; and increased crossing of optic fibers; bleeding diathesis due to a platelet storage pool deficiency; and deposition of lysosomal ceroid, which may cause pulmonary fibrosis (onset in the early thirties), granulomatous colitis (severe presentation in ~ 15% of all cases) and cardiomyopathy in some cases.  The clinical features of HPS are caused by the disruption of lysosome-related organelles in different tissue types.  The incidence of HPS is approximately 1 in 500,000-1,000,000.  HPS has an increased incidence, of up to 1 in 1800, in Puerto Rico. Locus heterogeneity has been associated with HPS and nine causative genes (HPS1-HPS9) have been identified to date. Pathogenic variants in the HPS4 (22q12.1) gene, account for approximately 12% of all cases in non-Puerto Rican populations.

References:  
  • GeneReviews
  • Wei & Li (2013). Pigm Cell Melanoma R, 26:176-192
  • OMIM #614073:  HPS
  • OMIM #606682:  HPS4 gene

Genes (1)

Indications

This test is indicated for:
  • Confirmation of a clinical diagnosis of HPS in an individual in whom sequence analysis was negative.
  • Carrier testing in adults with a family history of HPS in whom sequence analysis was negative.

Methodology

DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.

Detection

Detection is limited to duplications and deletions. The CGH array will not detect point or intronic pathogenic variants. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
Whole Blood (EDTA)
WBP

Requirements
EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.
DNA, Isolated
DNA

Requirements
Microtainer
3µg
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.

Special Instructions

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.
  • Sequence analysis of the HPS4 gene is available and is required before deletion/duplication analysis.  
  • Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
  • Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

How to Order