NGS-based 100-gene panel of hypopigmentation identifies mutations in Chinese Hermansky-Pudlak syndrome patients

Pigment Cell Melanoma Res. 2016 Nov;29(6):702-706. doi: 10.1111/pcmr.12534. Epub 2016 Oct 19.

Abstract

Hermansky-Pudlak syndrome (HPS) is a rare recessive disorder characterized by hypopigmentation, bleeding diathesis, and other symptoms due to multiple defects in lysosome-related organelles. Ten HPS subtypes have been identified with mutations in HPS1 to HPS10. Only four patients with HPS-1 have been reported in Chinese population. Using next-generation sequencing (NGS), we have screened 100 hypopigmentation genes and identified four HPS-1, two HPS-3, one HPS-5, and three HPS-6 in Chinese HPS patients with typical ocular or oculocutaneous albinism and the absence of platelet dense granules together with other variable phenotypes. All these patients except one homozygote were compound heterozygotes. Among these mutations, 14 were previously unreported alleles (four in HPS1, three in HPS3, two in HPS5, five in HPS6). Our results demonstrate the feasibility and utility of NGS-based panel diagnostics for HPS. Genotyping of HPS subtypes is a prerequisite for intervention of subtype-specific symptoms.

Keywords: Hermansky-Pudlak syndrome; albinism; lysosome-related organelles; next-generation sequencing; previouslyunreported alleles.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 3 / genetics
  • Adaptor Protein Complex beta Subunits / genetics
  • Adult
  • Biomarkers / analysis*
  • Carrier Proteins / genetics
  • Child
  • Child, Preschool
  • Female
  • Genotype
  • Hermanski-Pudlak Syndrome / diagnosis*
  • Hermanski-Pudlak Syndrome / genetics*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Hypopigmentation / genetics*
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Membrane Proteins / genetics
  • Mutation*
  • Pedigree

Substances

  • AP3B1 protein, human
  • Adaptor Protein Complex 3
  • Adaptor Protein Complex beta Subunits
  • Biomarkers
  • Carrier Proteins
  • HPS1 protein, human
  • HPS3 protein, human
  • HPS5 protein, human
  • HPS6 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins