Clinical Features and Novel Genetic Variants Associated with Hermansky-Pudlak Syndrome

Genes (Basel). 2022 Jul 20;13(7):1283. doi: 10.3390/genes13071283.

Abstract

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive syndromic form of albinism, characterized by oculocutaneous albinism (OCA) and other systemic complications. The purpose of this study was to investigate patients with HPS-associated gene mutations and describe associated ocular and extraocular phenotypes. Fifty-four probands clinically diagnosed as albinism were enrolled. Ophthalmic examinations and genetic testing were performed in all subjects. The phenotypic and genetic features were evaluated. HPS-associated gene mutation was identified in four of the patients with albinism phenotype. Clinically, photophobia, and nystagmus was detected in all (4/4) patients, and strabismus was found in one (1/4) patient. Fundus examination revealed fundus hypopigmentation and foveal hypoplasia in all (8/8) eyes. Eight novel causative mutations were detected in these four HPS probands. Five (62.5%, 5/8) of the mutations were nonsense, two of the mutations were missense (25%, 2/8), and one of the mutations was frameshift (12.5%, 1/8). All patients in our study carried compound heterozygous variants, and all these pathogenic variants were identified to be novel, with most (62.5%, 5/8) of the mutations being nonsense. Our results improved the understanding of clinical ocular features, and expanded the spectrum of known variants and the genetic background of HPS.

Keywords: Hermansky-Pudlak syndrome; clinical characteristics; genetic characteristics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Eye
  • Genetic Testing
  • Hermanski-Pudlak Syndrome* / diagnosis
  • Hermanski-Pudlak Syndrome* / genetics
  • Humans
  • Mutation
  • Phenotype

Grants and funding

This study is supported grants from the National Natural Science Foundation of China grant NSFC (subject number: 82070995), and the Fundamental Research Funds of the State Key Laboratory of Ophthalmology (subject number: 2022QN08). The funding organizations had no role in the design or conduct of this study.