X-linked ocular albinism (Nettleship-falls): a novel 29-bp deletion in exon 1. Carrier detection by ophthalmic examination and DNA analysis

Background: Mutations in the OA1 gene on the short arm of the X chromosome are known to cause X-linked ocular albinism (x1OA) in males. A four-generat ion family with this disorder, including asymptomatic carrier females, was investigated by molecular analysis of the OA1 gene. Methods: DNA samples we re available from 22 individuals of this family, including 6 affected males and 6 obligate carriers. The nine exons of the OA1 gene were amplified and further analyzed by SSCP and sequencing. Results: A detailed clinical exam ination of the index patient and two female carriers showed the typical sig ns of ocular albinism. Visual evoked potential responses showed markedly as ymmetrical responses from the two hemispheres in the affected person as wel l as in the carriers, as a result of misrouting and decussation of optic ne rve fibers. Molecular genetic analysis demonstrated a previously undescribe d 29-bp deletion at position 225-253 in exon 1 of the OA1 gene, which segre gated in the family. Conclusion: Clinical examination combined with molecul ar genetic analysis enhances the potential for a precise diagnosis for pers ons at risk of x1OA and provide an accurate basis for genetic counseling.