to depend on factors other than mutation alone (Forsius et al. 1973; Eksandh et al. 2005; Pimenides et al. 2005). Since RS1 exhibits complete penetrance (Forsius et al. 1973), the most likely theory is that modifier genes may play a role.

The small, six exon RS1 gene (Xp 22.2) is expressed only in retinal tissues and encodes the extracellular, 201-amino acid peripheral membrane protein, Retinoschisin (RS). Its function in photoreceptor membrane adhesion (Wu et al. 2005) is afforded by the highly conserved, 157 amino acid discoidin domain (DD; cys 63 to cys 219) present in many cell adhesion and cell signalling proteins (Wu and Molday 2003; Wu et al. 2005; Molday et al. 2007).

XLRS pathology predominantly arises from missense mutations in exons four to six (The Retinoschisis Consortium 1998; Hewitt et al. 2005) often causing protein misfolding and intracellular retention and degradation (Wang et al. 2002).

With the liklihood of successful human gene therapy in the forseeable future, it is our aim at the Australian Inherited Retinal Disease Register and DNA Bank to progressively expand the once Western Australian specific database (est. 1984) and DNA bank (est. 2001), to include all Australian families affected inherited retinal disease (IRD). This now rapidly growing database currently contains information on 2300 individuals dating back to 1976, and includes results of electrophysiological, psychophysical and ophthalmic tests, family and personal history details, best known diagnoses, and more recently, disease causing mutations. Information and DNA will be made available to approved researchers and we anticipate that in time, the resource may contribute to the improvement of diagnostic and prognostic accuracy and help guide Australian patients for future therapies as well as funding towards research most applicable to the Australian IRD community.

With our initial focus on Retinoschisis, Stargardt’s disease, autosomal dominant retinitis pigmentosa, and Leber’s congenital amaurosis we recently undertook to first analyse genomic DNA of Western Australian families for disease causing mutations. The small Retinoschisis study is presented here.

32.2 Methodology

Four of five Western Australian families on the IRD Register, containing individuals clinically diagnosed with XLRS who had not before participated in similar research were included in the study. Informed consent was obtained from all research participants in accordance with Sir Charles Gairdner Hospital Human Research Ethics Committee’s approval guidelines.

32.2.1 Molecular Genetic Studies

Blood (30mL EDTA) and saliva samples (Oragene Saliva Kit) were collected from 10 individuals clinically diagnosed with XLRS and their family members. Genomic