Amelanotic/hypopigmented melanoma in a sibship with oculocutaneous albinism

Abstract

Oculocutaneous albinism (OCA) comprises a group of heterogeneous disorders characterized by hypopigmentation of the skin, eyes, and hair secondary to decreased/absent melanin. 1 OCA is caused by autosomal recessive variants in genes impacting the melanin biosynthesis (TYR, OCA2, TYRP1, SLC45A2, SLC24A5, and C10orf11 2 ). Clinical subtypes of OCA correlate with degrees of pigmentation (OCA1A, OCA1B, OCA2, OCA3, and OCA4), where the most severe form, OCA1A, is characterized by complete lack of melanin production. 2 Melanin deficiency makes OCA-affected individuals more vulnerable to basal cell and squamous cell carcinomas. 2 Melanomas rarely occur in OCA, accounting for ~1% of skin malignancies. 2 Rarer still is the co-occurrence of multiple primary melanomas (MPM) and OCA. 3 When individuals with OCA develop melanoma, it is typically in the amelanotic/hypopigmented (AHM) form, 3 which is conversely rare in the general population. 4This study describes three siblings with OCA1B where two sisters were diagnosed with primary AHM and their brother had no melanoma history. Filtering whole-exome sequencing (WES) data for variants in OCA and/or melanoma susceptibility genes, we aimed to identify variants segregating with the melanoma phenotype. Three-dimensional (3D) total-body