PURPOSE: To elucidate the molecular basis of oculocutaneous albinism with variable expressivity in a family from The Netherlands in which no consanguinity was reported. METHODS: Three affected family members were screened for mutations in tyrosinase (TYR) and the pink-eye-dilution gene (P) by using SSCP. The melanocortin receptor gene (MC1R) and amplimers of P showing an aberrant banding pattern in SSCP were analyzed by direct sequencing. All participants underwent ophthalmologic examination including funduscopy, and visually evoked potentials were recorded in two cases. RESULTS: The pedigree had three branches A, B, and C. We identified three mutations in P (V443I, N476S, C793F) that cause a compound heterozygous situation in cases from branch A (N476S/C793F) and B (V443I/C793F), who showed oculocutaneous albinism. Hair and skin color followed the light Nordic complexion that was also present in other affected and unaffected members of this family. Descendants of branches A and B showed light complexion with iris translucency and peripheral fundus hypopigmentation independent from the genotype identified. A single descendant had red hair, carrying a well known compound MC1R mutation combination for red hair color and a single heterozygous P mutation. CONCLUSIONS: P mutations underlie oculocutaneous albinism in this family. Two known mutations in MC1R caused red hair color in one family member. No modifier effect of MC1R on P mutations could be deduced from the results of this study.
PURPOSE: To elucidate the molecular basis of oculocutaneous albinism with variable expressivity in a family from The Netherlands in which no consanguinity was reported. METHODS: Three affected family members were screened for mutations in tyrosinase (TYR) and the pink-eye-dilution gene (P) by using SSCP. The melanocortin receptor gene (MC1R) and amplimers of P showing an aberrant banding pattern in SSCP were analyzed by direct sequencing. All participants underwent ophthalmologic examination including funduscopy, and visually evoked potentials were recorded in two cases. RESULTS: The pedigree had three branches A, B, and C. We identified three mutations in P (V443I, N476S, C793F) that cause a compound heterozygous situation in cases from branch A (N476S/C793F) and B (V443I/C793F), who showed oculocutaneous albinism. Hair and skin color followed the light Nordic complexion that was also present in other affected and unaffected members of this family. Descendants of branches A and B showed light complexion with iris translucency and peripheral fundus hypopigmentation independent from the genotype identified. A single descendant had red hair, carrying a well known compound MC1R mutation combination for red hair color and a single heterozygous P mutation. CONCLUSIONS: P mutations underlie oculocutaneous albinism in this family. Two known mutations in MC1R caused red hair color in one family member. No modifier effect of MC1R on P mutations could be deduced from the results of this study.
Authors: Mohsin Shahzad; Sairah Yousaf; Yar M Waryah; Hadia Gul; Tasleem Kausar; Nabeela Tariq; Umair Mahmood; Muhammad Ali; Muzammil A Khan; Ali M Waryah; Rehan S Shaikh; Saima Riazuddin; Zubair M Ahmed Journal: Sci Rep Date: 2017-03-07 Impact factor: 4.379
Authors: Caroline F Wright; Ben West; Marcus Tuke; Samuel E Jones; Kashyap Patel; Thomas W Laver; Robin N Beaumont; Jessica Tyrrell; Andrew R Wood; Timothy M Frayling; Andrew T Hattersley; Michael N Weedon Journal: Am J Hum Genet Date: 2019-01-18 Impact factor: 11.025