gms | German Medical Science

Introducing new techniques of analysis like polymerase chain reaction (PCR), Fluorescence In-situ Hybridisation (FISH), and Microarray-Chips has revolutionised and automated genetic diagnostics in the past 20 years. An increasing number of diseases of all parts of the eye are being correlated with hereditary causes showing obvious correlations in monogenic disorders as well as less obvious correlations in multifactorial and polygenic disorders.

Knowledge of the molecular causes and genotype-phenotype correlation is not necessarily applied to molecular diagnostics. For many monogenic disorders high locus heterogeneity is disclosed, and although gene by gene is reported, it becomes obvious that a complete elucidation of all genetic causes may not be possible feasible. The problem increases since prime reports of genetic causes of a disorder like Retinitis pigmentosa (RP) usually cover those genes with the highest prevalence in this disorder. Each additional gene covers a decreasing fraction of these disorders until finally a new gene in a recessive disorder is described in only one or two extended families, and further independent affected individuals will rarely be found. Further studies in these rare genes cause problems to the diagnostic centres for two reasons. On the one hand detection of mutations in disorders of high locus heterogeneity costs money that is provided by the health care system only for certain conditions. On the other hand research results are more prestigious and scientific constraints urge the expert centres to invest their power into new topics.

Currently, direct benefit of molecular diagnostics is not always obvious. Knowledge of genetic causes is however mandatory to develop treatment opportunities and to evaluate therapeutic trials.