Hermansky-Pudlak Syndrome Panel (9 Genes) Test Details
The Hermansky-Pudlak syndrome panel sequences 9 genes associated with Hermansky-Pudlak syndrome (HPS). HPS is a rare, autosomal recessive genetic condition associated with by platelet deficiency, oculocutaneous albinism, visual impairment, nystagmus, and pulmonary fibrosis. As a group, HPS has an estimated prevalence of 1:500,000 in the general population but has a higher prevalence in the Puerto Rican population (1:1,800), with HPS1 and HPS3 as the most common subtypes (www.genetests.org).
Hermansky-Pudlak syndrome - BLOC1S3, BLOC1S6, DTNBP1, HPS3, HPS5, HPS6
Hermansky-Pudlak syndrome & Pulmonary Fibrosis - AP3B1, HPS1, HPS4
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|AP3B1||Adaptor-Related Protein Complex 3, Beta 1 Subunit||603401||5q14.1|
|BLOC1S3||Biogenesis Of Lysosomal Organelles Complex-1, Subunit 3||609762||19q13.32|
|BLOC1S6||Biogenesis Of Lysosomal Organelles Complex-1, Subunit 6, Pallidin||604310||15q21.1|
|DTNBP1||Dystrobrevin-Binding Protein 1||607145||6p22.3|
|HPS1||Hermansky-Pudlak Syndrome 1||604982||10q23.1-q23.3|
|HPS3||Hermansky-Pudlak Syndrome 3||606118||3q24|
|HPS4||Hermansky-Pudlak Syndrome 4||606682||22cen-q12.3|
|HPS5||Hermansky-Pudlak Syndrome 5||607521||11p14|
|HPS6||Hermansky-Pudlak Syndrome 6||607522||10q24.32|
The Hermansky-Pudlak Panel should be ordered for individuals with a diagnosis or suspected diagnosis of Hermansky-Pudlak syndrome. This panel will provide comprehensive coverage of the implicated genes and minimize the incidence of variants of unknown significance compared with the PulmoGene panel.
We recommend careful consideration when deciding whether to order the full panel or the disease-specific sub-panels. For clinically complex cases where the diagnosis is not clear, the complete multi-disease panel may shorten the “testing odyssey.” However, it should be noted that large multi-disease panels typically come with an increased risk of an inconclusive result, as many genes have not yet been sufficiently interrogated for all included diseases. Disease-specific sub-panels may, therefore, be the better first line test for individuals with clear clinical diagnoses.
This test is performed by next-generation sequencing, using Agilent SureSelect capture, followed by sequencing of the coding regions and splice sites, using Illumina sequencing technologies. Variant calls are generated, using the Burrows-Wheeler Aligner, followed by Genomic Analysis Tool Kit (GATK) analysis. Detection of copy number variants (CNVs) encompassing 1 or more exons is performed, using VisCap™ analysis. Sanger sequencing is used to fill in regions with insufficient coverage. All clinically significant variants are confirmed by Sanger sequencing or droplet digital PCR. Variants classified as likely benign or benign are not confirmed. This test does not detect variants in non-coding regions that could affect gene expression, aside from the splice junctions, and a few exons have been excluded due to technical difficulties. CNV analysis is only performed when data meets necessary quality standards and may not be available for all cases.
Analytical and Clinical Sensitivity
This test is 100.00% sensitive (525/525 variants tested; 95% CI = 99.27-100.00% ) to detect variants changing a single base and 100.00% sensitive to detect insertion/deletions 1-21 bp in size (17/17 variants tested; 95% CI = 81.57-100.00%). Regions with high sequence homology are included in this test if a unique Sanger sequencing assay can be designed to rule out false positive calls. Analytical sensitivity in these regions may be reduced.
Given the recent launch of this disease area, the detection rate for the Hermansky-Pudlak Syndrome Panel remains unknown at this point.
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