Abstract
Oculocutaneous albinism (OCA) is a group of Mendelian disorders characterized by hypopigmentation of skin, hair and pigmented ocular structures. While much of the genetic heterogeneity of OCA has been resolved, many patients still lack a molecular diagnosis following exome sequencing. Here, we report a consanguineous family in which the index patient presented with OCA and Hirschsprung disease but tested negative for known genetic causes of OCA. Instead, he was found to have a homozygous presumptive loss of function variant in PMEL. PMEL encodes a scaffolding protein that is essential for the normal maturation of melanosomes and normal deposition of the melanin pigment therein. Numerous PMEL vertebrate ortholog mutants have been reported and all were characterized by conspicuous pigmentary abnormalities. We suggest that the patient we report is the first human equivalent of PMEL loss of function.