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M.N. Preising, A. Plomp, H. Forster, B. Lorenz; Albinism in a Dutch Family Due to Triallelic Inheritance of Mutations in P and MC1R . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3821.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:A three generation Dutch family with albinism patients in three branches (three brothers married to three unrelated females) was investigated for mutations in the pink–eye–dilution (P) and melanocortin receptor gene (MC1R) based on a recent publication by King et al. (AJHG 73:638, 2003). Methods:DNA was extracted from peripheral blood samples from three unaffected parents, three affected and two unaffected children of both sexes from two branches of a Dutch family. P exons were amplified with previously published primers and subjected to SSCP screening. MC1R was amplified in two amplimers by primers designed by the authors and sequenced directly. Patients underwent general clinical diagnostics including visual acuity testing, funduscopy, and VEP in the affected probands. Results:We identified two disease causing mutations in P (N476S, C793F) in two affected individuals in one branch of the family (766.5 and 766.6), showing C793F to segregate with the paternal and N476S with the maternal side. The affected daughter (766.7) from the second branch and her unaffected father (766.3) carried C793F only. Screening of MC1R revealed three missense mutations (V60L, G104S, and R160W). R160W was present in both branches of the family and in all affected and three unaffected family members. V60L and G104S were present on different alleles of the mother of branch two and only V60L was inherited by her unaffected son (766.8) while her daughter (766.7) carried G104S. The siblings from the first branch showed nystagmus, light skin and blond hair, pronounced iris translucency, hypopigmented fundi, VEP misrouting, and a VA of 0.2 in the better eye. Patient 766.7 followed this description but her hair was darker, her irides showed pigmentation, and her VA was 0.3 in the better eye. Conclusions:Here we show for the first time that triallelic inheritance for mutations in P and MC1R occurs in albinism patients. Branch 1 of the investigated family is affected by albinism due to P mutations modified by R160W in MC1R which causes a severe form of albinism. Patient 766.7 in branch 2 has a predisposition by single heterozygosity for C793F in P. In addition, she carries R160W and G104S in MC1R in the compound heterozygous state. This condition causes albinism with residual ability to develop pigmentation. Her mother and brother who are only compound heterozygous for MC1R mutations do not show signs of albinism nor does her father who carries single heterozygous mutations in both genes.
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