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. 2020 Mar;41(3):543-580.
doi: 10.1002/humu.23968. Epub 2020 Jan 23.

Hermansky-Pudlak syndrome: Mutation update

Marjan Huizing  1 , May C V Malicdan  1 , Jennifer A Wang  1 , Hadass Pri-Chen  1   2 , Richard A Hess  1 , Roxanne Fischer  1 , Kevin J O'Brien  3 , Melissa A Merideth  3 , William A Gahl  1 , Bernadette R Gochuico  1
Affiliations

Hermansky-Pudlak syndrome: Mutation update

Marjan Huizing et al. Hum Mutat. 2020 Mar.

Abstract

Hermansky-Pudlak syndrome (HPS) is a group of 10 autosomal recessive multisystem disorders, each defined by the deficiency of a specific gene. HPS-associated genes encode components of four ubiquitously expressed protein complexes: Adaptor protein-3 (AP-3) and biogenesis of lysosome-related organelles complex-1 (BLOC-1) through -3. All individuals with HPS exhibit albinism and a bleeding diathesis; additional features occur depending on the defective protein complex. Pulmonary fibrosis is associated with AP-3 and BLOC-3 deficiency, immunodeficiency with AP-3 defects, and gastrointestinal symptoms are more prevalent and severe in BLOC-3 deficiency. Therefore, identification of the HPS subtype is valuable for prognosis, clinical management, and treatment options. The prevalence of HPS is estimated at 1-9 per 1,000,000. Here we summarize 264 reported and novel variants in 10 HPS genes and estimate that ~333 Puerto Rican HPS subjects and ~385 with other ethnicities are reported to date. We provide pathogenicity predictions for missense and splice site variants and list variants with high minor allele frequencies. Current cellular and clinical aspects of HPS are also summarized. This review can serve as a manifest for molecular diagnostics and genetic counseling aspects of HPS.

Keywords: albinism; biogenesis of lysosome-related organelles; bleeding diathesis; granulomatous colitis; hypopigmentation; pulmonary fibrosis.

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Conflict of interest statement

Disclosure statement: The authors declare no conflicts of interest.

Figures

Figure 1:
Figure 1:
Distribution of HPS1 Gene Variants
Figure 2:
Figure 2:
Distribution of AP3B1 Gene Variants
Figure 3:
Figure 3:
Distribution of HPS3 Gene Variants
Figure 4:
Figure 4:
Distribution of HPS4 Gene Variants
Figure 5:
Figure 5:
Distribution of HPS5 Gene Variants
Figure 6:
Figure 6:
Distribution of HPS6 Gene Variants
Figure 7:
Figure 7:
Distribution of BLOC1S8 (HPS-7), BLOC1S3 (HPS-8), BLOC1S6 (HPS-9), and AP3D1 (HPS-10) Gene Variants
See this image and copyright information in PMC

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