Albinism is a pigment disorder affecting eye, skin and/or hair. Patients usually have decreased melanin in affected tissues and suffer from severe visual abnormalities, including foveal hypoplasia and chiasmal misrouting. Combining our data with those of the literature, we propose a single functional genetic retinal signalling pathway that includes all 22 currently known human albinism disease genes. We hypothesise that defects affecting the genesis or function of different intra-cellular organelles, including melanosomes, cause syndromic forms of albinism (Hermansky-Pudlak (HPS) and Chediak-Higashi syndrome (CHS)). We put forward that specific melanosome impairments cause different forms of oculocutaneous albinism (OCA1-8). Further, we incorporate GPR143 that has been implicated in ocular albinism (OA1), characterised by a phenotype limited to the eye. Finally, we include the SLC38A8-associated disorder FHONDA that causes an even more restricted “albinism-related” ocular phenotype with foveal hypoplasia and chiasmal misrouting but without pigmentation defects. We propose the following retinal pigmentation pathway, with increasingly specific genetic and cellular defects causing an increasingly specific ocular phenotype: (HPS1-11/CHS: syndromic forms of albinism)-(OCA1-8: OCA)-(GPR143: OA1)-(SLC38A8: FHONDA). Beyond disease genes involvement, we also evaluate a range of (candidate) regulatory and signalling mechanisms affecting the activity of the pathway in retinal development, retinal pigmentation and albinism. We further suggest that the proposed pigmentation pathway is also involved in other retinal disorders, such as age-related macular degeneration. The hypotheses put forward in this report provide a framework for further systematic studies in albinism and melanin pigmentation disorders.

白化病是一种影响眼睛、皮肤和/或头发的色素障碍。患者通常在受影响的组织中黑色素减少，并患有严重的视觉异常，包括中心凹发育不全和视交叉错误。将我们的数据与文献数据相结合，我们提出了一个单一的功能性遗传视网膜信号通路，其中包括所有 22 个目前已知的人类白化病基因。我们假设影响不同细胞内细胞器（包括黑素体）的起源或功能的缺陷会导致白化病的综合征形式（Hermansky-Pudlak (HPS) 和 Chediak-Higashi 综合征 (CHS)）。我们提出特定的黑素体损伤会导致不同形式的眼皮肤白化病 (OCA1-8)。此外，我们合并了GPR143这与眼部白化病 (OA1) 有关，其特征是仅限于眼睛的表型。最后，我们包括SLC38A8-相关疾病 FHONDA，导致更加局限的“白化病相关”眼表型，伴有中心凹发育不全和视交叉错误，但没有色素沉着缺陷。我们提出以下视网膜色素沉着途径，随着越来越具体的遗传和细胞缺陷导致越来越具体的眼表型：（HPS1-11/CHS：白化病的综合征形式）-（OCA1-8：OCA）-（GPR143：OA1）-（ SLC38A8：本田）。除了疾病基因的参与，我们还评估了影响视网膜发育、视网膜色素沉着和白化病通路活动的一系列（候选）调节和信号机制。我们进一步表明，拟议的色素沉着途径也涉及其他视网膜疾病，例如年龄相关性黄斑变性。