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.

Objectives: Oculocutaneous albinism (OCA), a group of inherited disorders characterized by deficient melanin synthesis, leads to hypopigmentation of the skin, hair, and eyes. OCA type 2 (OCA2) is caused by mutations in OCA2. This study aimed to characterize the comprehensive clinical and genetic spectrum of OCA2, and to identify the key ocular determinants of visual acuity. Methods: We enrolled 90 probands clinically diagnosed with albinism. Whole-exome sequencing and comprehensive ophthalmic examinations were performed. Results: OCA2 was confirmed in 29 probands (32.2%). Visual impairment was distributed as mild/no impairment (30.8%), moderate (53.8%), and severe/blindness (15.4%). All patients exhibited nystagmus and photophobia. Ocular phenotype grading showed distinct distributions: iris translucency (n = 25) was 68% grade 3, 20% grade 2, 8% grade 1, and 4% grade 4; fundus hypopigmentation (n = 26) was 42.3% grade 1, 30.8% grade 2, and 26.9% grade 3; and foveal hypoplasia (n = 20) was 70% grade 4, 25% grade 3, and 5% grade 1. We identified 33 OCA2 variants (26 compound heterozygous and 3 homozygous), with missense variants accounting for 62.1% of alleles. Five variants were identified to be novel. The severity of foveal hypoplasia demonstrated a strong, statistically significant negative correlation with visual acuity (r = −0.71, p < 0.001). Conclusions: OCA2 accounts for 32.2% of albinism cases, with moderate visual impairment being the most common (53.8%). Graded phenotyping demonstrated moderate-to-severe iris translucency (88%), mild fundus hypopigmentation (42.3%), and severe (grade 4) foveal hypoplasia (70%). The severity of foveal hypoplasia emerged as an important determinant of visual acuity.