Genetic studies of ocular albinism in a large Virginia kindred

Nettleship-Falls ocular albinism is an X-linked disorder characterized by variable degrees of impaired visual acuity, nystagmus, and macular hypoplasia in affected males and variable fundus pigmentation but normal acuities in females. Because of extreme variability in clinical manifestation, examination of family members may be necessary to confirm the diagnosis and is essential for genetic counseling purposes. This study reports the pedigree analysis and clinical findings in a large kindred from rural Virginia with 31 males reported to be affected among the 287 individuals in the pedigree. Clinical findings were quite variable, even within sibships, and some cases had been previously misdiagnosed, even in the presence of this remarkable family history. Linkage analysis in this family did not show the expected linkage with the Xg blood group. Examination of skin biopsies clearly indicated the cutaneous abnormality of giant pigment melanosomes (GPM) in both affected males and carrier females. Our use of light microscopy for detection of characteristic GPM may be easily employed as a carrier detection test, and therefore, provide the basis for accurate genetic counseling in families with ocular albinism.