Identification of P gene mutations in individuals with oculocutaneous albinism in sub‐Saharan Africa

Oculocutaneous albinism (OCA) is an inherited disorder resulting in hypopigmentation of the skin, hair, and eyes. OCA type 2 (tyrosinase‐positive) is the most common recessively inherited disorder among southern African Blacks. OCA2 is also seen in southern African Caucasoids, but is less frequent. The gene responsible for this type of albinism, P, is the human homolog of the mouse pink‐eyed dilution gene. Mutations at this locus are also responsible for the milder hypopigmentation phenotype seen in individuals with brown oculocutaneous albinism (BOCA). A common African P mutation was identified in Black OCA2 individuals, and has since been shown to occur in Black individuals with brown OCA as well. This mutation is a 2.7 kb interstitial deletion. In this study, we undertook to screen the coding region of the P gene for mutations in the non‐2.7 kb deletion alleles of OCA2 patients who did not carry the deletion allele in either one or both of their P genes. We identified four mutations (A334V, 614delA, 683insT, 727insG) in a group of 39 unrelated Black OCA2 patients with a total of 52 non‐2.7 kb deletion OCA2 genes. When taking all OCA2 cases into consideration, including those homozygous for the 2.7 kb deletion mutation, these account for a further 1.7% of OCA2 mutations in southern African Blacks, increasing the overall mutation detection rate to 78.7%. Three mutations (E678K, L688F, I370T) were identified in a group of 15 Black patients with an initially unclassified type of OCA and another three mutations (IVS 14‐2 (a→g), V350M, P743L) were identified in nine Caucasoid OCA patients. Relatively few mutations, all with low frequency, were identified in the non‐2.7 kb deletion OCA genes. We propose that other mutations may lie either within intronic sequence or within the promoter region of the gene. Hum Mutat 15:166–172, 2000. © 2000 Wiley‐Liss, Inc.