Clinical and Genetic Studies of X-Linked Juvenile Retinoschisis

Objectives:

The overall goal of this protocol is to better understand the etiology of XLRS disease to facilitate further research to identify a potential treatment for the disease. The specific primary objectives of this study are to:

• Investigate the relationship between genotype and phenotype in X-Linked Retinoschisis by correlating four phenotype severity classes with two classes of genotypes. This is the first step in developing a comprehensive genotypephenotype

correlation.

• Characterize the anatomical and functional characteristics of retinoschisis to refine the phenotype scale and investigate and characterize specific XLRS1 mutations to generate a well-documented genotype-phenotype correlation map.

With the opportunity to study the genotypes and phenotypes of many affected males and the genotype of family members, a secondary objective of this study will be to develop a detailed pedigree for affected families. This information may be used to develop preliminary risk estimates for potential carrier females.

Study Population:

Up to 500 participants may enroll in this study. A minimum of 150 of participants are expected to be males diagnosed with X-Linked Retinoschisis. Participants may be recruited from the NIH and also from participating off-site locations. The quality of the genetic observation is directly proportional to the number of affected individuals and genetically-different families enrolled.

Design:

This natural history, multi-center, registry study to enroll males diagnosed with X-Linked Retinoschisis and the family members of affected individuals. Onsite affected males will undergo clinical examination and have their blood drawn for genotyping. Onsite unaffected participants will undergo eye examinations. Blood may also be drawn from the onsite unaffected participants but this is not required. Sites outside of NIH are participating as referral centers to accumulate the cohort. Offsite affected male participants will forward a blood sample and records from previous eye examinations to the NEI for review and analysis. Offsite unaffected participants will forward records from previous eye examinations and may provide a blood sample although this is not required.

Outcome Measures:

The primary outcome is the categorization of the proband s genotype and phenotype and determination of the relationship between the two.

• INCLUSION CRITERIA:

Eligible participants must satisfy one of the criteria below:

• Male diagnosed with X-Linked Juvenile Retinoschisis (proband). A proband will be defined as the first X-Linked Juvenile Retinoschisis diagnosed male in a given family who contacts the NIH for participation in the study; or
• Female who is a suspected carrier (i.e., mother of proband); or
• Other relative of proband including affected and unaffected males and females.

The participant (or the participant s legal guardian) understands and signs this protocol s informed consent document and minor participants between the ages of 7 and 17 must provide assent.

Exclusion criteria

Affected males will be ineligible for participation if:

• The participant has a significant media opacity or other obstruction precluding a complete fundus examination including retinal photography.
• The participant is unwilling or unable to contribute a blood sample for genotyping if there is not existing genetic analysis data from a documented family member.

Both affected and unaffected individuals will be ineligible for participation if:

• The participant is younger than two years (seen at the NIH) or younger than nine months (participating offsite through medical record review and blood submission).
• The participant is unable to cooperate with study procedures without anesthesia.