Juvenile retinoschisis: a model for diagnostic testing of x-linked ophthalmic disease. Trans Am Ophthalmol Soc 1999;97:451–464.

X-linked juvenile retinoschisis (RS) provides a starting point to define clinical paradigms and understand the limitations of diagnostic molecular testing. The RS phenotype is specific, but the broad severity range is clinically confusing. Molecular diagnostic testing obviates unnecessary examinations for boys at-risk and identifies carrier females who otherwise show no clinical signs. The XLRS1 gene has 6 exons of 26-196 base-pair size. Each exon was amplified by a single polymerase chain reaction and then sequenced, starting with exons 4 through 6, which contain mutation “hot spots.” The 6 XLRS1 exons were sequenced serially. If alterations were found, they were compared with mutations in the over 120 XLRS families and with the over 300 mutations reported worldwide. Point mutations, small deletions, or rearrangements were identified in nearly 90% of males with a clinical diagnosis of RS. XLRS1 has very few sequence polymorphisms. Carrier-state testing produced one of three results: (1) positive, in which the woman had the same mutation as an affected male relative or known in other RS families; (2) negative, in which she lacked the mutation of her affected male relative; and (3) uninformative, in which no known mutation was identified or no information existed about the familial mutation. The authors conclude that molecular RS screening is an effective diagnostic tool that complements the clinician’s skills for early detection of at-risk males.—Thomas J. Liesegang.