Abstract: Objective To analyze the genetic and clinical characteristics of Chinese patients with albinism-related gene variants, and to compare the clinical manifestations between ocular albinism (OA1) and oculocutaneous albinism (OCA). Design Retrospective case series. Participants 32 patients (from 28 families) with pathogenic variants in albinism-related genes collected from Beijing Tongren Hospital. Methods All patients underwent detailed ophthalmic examinations, including best-corrected visual acuity (BCVA), anterior segment photography, color fundus photography and optical coherence tomography (OCT). The pigmentation of skin and hair was also recorded. Genomic DNA was extracted from peripheral venous blood samples of the proband, his immediate family members and affected family members. Sanger sequencing, targeted exome sequencing (TES) and real-time quantitative polymerase chain reaction (PCR) was used to identify pathogenic variants. Multiple bioinformatics analysis software was used to predict the pathogenicity of the variants and co-segregation verification was performed. Main Outcome Measures Pathogenic variants, BCVA, nystagmus, foveal hypoplasia (FH) grade, pigmentation of eye, skin and hair. Results A total of 33 pathogenic variants in 7 genes (GPR143, OCA2, TYR, LRMDA, HPS1, HPS6 and SLC45A2) were detected in 32 patients, of which 8 were novel variants. There were 18 OA1 patients with GPR143 gene variants and 14 OCA patients with the other 6 genes variants. These patients all had varying degrees of vision loss, fundus hypopigmentation and FH. All but two patients had congenital nystagmus. The iris color of OA1 patients was darker, the FH grade was mainly 1~2, and no skin or hair hypopigmentation was found. OCA patients had diverse iris and fundus pigmentation, and most of them had varying degrees of skin and hair hypopigmentation. Patients with syndromic OCA were also associated with blood or immune system abnormalities. The two patients without nystagmus had mild visual impairment and FH. There were significant differences in iris and fundus pigmentation between OA1 patients and OCA patients. Conclusion This study preliminarily described the pathogenic gene composition of Chinese patients with albinism and expanded the variant spectrum of each gene. It was found that the degree of iris hypopigmentation was mild in OA1 patients, while the ocular and systemic pigmentation was highly variable in OCA patients. No obvious genotype-phenotype relationship was found. Genetic testing is essential for definitive diagnosis of atypical patients. (Ophthalmol CHN, 2023, 32: 182-191)

Key words: ocular albinism, oculocutaneous albinism, gene variant