title: Mutation analysis in a family with oculocutaneous albinism manifesting in the same generation of three branches.
abstract: OBJECTIVE
  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.affiliation: Regensburg University Medical Center, Department of Pediatric Ophthalmology, Strabismology and Ophthalmogenetics, Franz Josef Strauss, Regensburg, Germany. mpreising@arcor.de
authors.forename: Markus N
authors.initials: MN
authors.lastname: Preising
authors.forename: Hedwig
authors.initials: H
authors.lastname: Forster
authors.forename: H
authors.initials: H
authors.lastname: Tan
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Astrid S
authors.initials: AS
authors.lastname: Plomp
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016115:Albinism, Oculocutaneous / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005654:Fundus Oculi; D006200:Hair Color; D006579:Heterozygote; D006801:Humans; D007498:Iris / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012880:Skin Pigmentation
chemical_list: D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; D044102:Receptor, Melanocortin, Type 1