Current landscape of Oculocutaneous Albinism in Japan

Abstract

Oculocutaneous albinism (OCA), which is roughly divided into non‐syndromic and syndromic OCA, is a group of autosomal recessive disorders caused by mutations in genes associated with pigmentation. Patients with OCA have hypopigmentation and ocular manifestations such as photophobia, amblyopia, and nystagmus. Hermansky–Pudlak syndrome (HPS), the most common syndromic OCA, is characterized by the additional features of a bleeding tendency and other critical systemic comorbidities such as pulmonary fibrosis and immunodeficiency. NGS‐based gene analyses have identified several new causative genes for OCA and have detected rare subtypes of OCA with high accuracy including Japanese patients. In our survey of 190 Japanese OCA patients/families, OCA4 is the most common subtype (25.3%) followed by OCA1 (20.0%), HPS1 (14.7%), and OCA2 (8.4%). Similar to the A481T variant in OCA2, which is associated with a mild form of OCA2 and skin color variation, the c.‐492_489delAATG variant located in the promoter region of SLC45A2 has been uniquely identified in Japanese patients with a mild form of OCA4. Further, rare OCA subtypes, including OCA3, HPS2, HPS3, HPS4, HPS5, HPS6, and HPS9, have also been identified in Japanese patients. The clinical characteristics and underlying molecular mechanisms of each subtype of OCA are concisely summarized in this review.

Genetics of non‐syndromic and syndromic oculocutaneous albinism in human and mouse

“…Oculocutaneous albinism type 4 (OCA4) is the most common type of albinism in Japan (Inagaki et al., 2004; Okamura & Suzuki, 2021) but rare (1:100,000) in the rest of the world. OCA4 is caused by mutations in the SLC45A2 gene (Newton et al., 2001).…”

“…Recently, a review article reported the genetic analyses of 190 individuals or their family members who were clinically suspected OCA in Japan from 2007 to 2019 (Okamura & Suzuki, 2021). Among them, 54.7% of individuals (104 out of 190) were diagnosed as non‐syndromic OCA, while 21.6% (41 out of 190) were syndromic OCA.…”

“…In Europe and North America, the frequency of albinism is in the range of 1:10,000–20,000. Currently, we know about at least 21 genes whose mutations are associated with the reported 22 different types of albinism (Garrido et al., 2021; Montoliu & Kelsh, 2014; Montoliu & Marks, 2017; Montoliu et al., 2014; Okamura & Suzuki, 2021). The largest group of people with albinism correspond to oculocutaneous albinism (OCA) (Grønskov et al., 2007).…”

Role of Amine Neurotransmitters and Their Receptors in Skin Pigmentation: Therapeutic Implication

“…Only the skin, hair, and eyes, or sometimes only the eyes, are affected [ 16 ]. There are four main types of OCA-OCA1 (TYR), OCA2 (OCA2), OCA3 (TRP1), and OCA4 (SLC45A2) [ 67 ]. In addition, albinism is observed as a symptom of various genetic diseases.…”

A custom capture sequence approach for oculocutaneous albinism identifies structural variant alleles at the OCA2 locus

“…A variety of exon‐targeted sequencing approaches have been critical in identifying OCA variant alleles in diverse populations. However, 10%–25% of OCA individuals remain without a definitive, biallelic diagnosis (Grønskov et al, 2019; Kruijt et al, 2018; Lasseaux et al, 2018; Okamura & Suzuki, 2020; Simeonov et al, 2013; Wei et al, 2010; Zhong et al, 2019). Included in this subset are many individuals for whom only one deleterious allele is identified.…”