Chapter 32

Genotypic Analysis of X-linked Retinoschisis

in Western Australia

Tina Lamey, Sarina Laurin, Enid Chelva, and John De Roach

Abstract X-linked Retinoschisis is a leading cause of juvenile macular degeneration. Four Western Australian families affected by X-Linked Retinoschisis were analysed using DNA and clinical information from the Australian Inherited Retinal Disease (IRD) Register and DNA Bank. By direct sequencing of the RS1 gene, three genetic variants were identified; 52+1G > T, 289T > G and 416delA. 289T > G has not been previously reported and is likely to cause a substitution of a membrane binding residue (W92G) in the functional discoidin domain. All clinically diagnosed individuals showed typical electronegative ERGs. The 52+1G > T obligate carrier also recorded a bilaterally abnormal rod ERG and mildly abnormal photopic responses. mfERG trace arrays showed reduced response densities in the paramacular region extending futher temporally for each eye.

Further analyses are currently underway for Stargardt’s disease, autosomal dominant and autosomal recessive retinitis pigmentosa, and Leber’s congenital amaurosis.

32.1 Introduction

Juvenile X-linked Retinoschisis (XLRS) is a common form of inherited juvenile macular degeneration caused by mutations in the Retinoschisin (RS1) gene (Forsius et al. 1973; George et al. 1995). Symptoms caused by splitting of inner and sometimes peripheral retinal layers typically present between 5 and 10 years of age and progress mildly until the 4th decade of life followed by more progressive deterioration (Deutman 1971; Kellner et al. 1990). Disease severity and progression exhibit significant variability even between affected siblings, hence they are likely

T. Lamey (B)

Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, 6009, Australia

e-mail: john.deroach@health.wa.gov.au

Medicine and Biology 664, DOI 10.1007/978-1-4419-1399-9_32,C Springer Science+Business Media, LLC 2010