Discovery of biomarkers in rare diseases: innovative approaches by predictive and personalized medicine

There are more than 8000 rare diseases (RDs) that affect >5 % of the world's population. Many of the RDs have no effective treatment and lack of knowledge creates delayed diagnosis making management difficult. The emerging concept of the personalized medicine allows for early screening, diagnosis, and individualized treatment of human diseases. In this context, the discovery of biomarkers in RDs will be of prime importance to enable timely prevention and effective treatment. Since 80 % of RDs are of genetic origin, identification of new genes and causative mutations become valuable biomarkers. Furthermore, dynamic markers such as expressed genes, metabolites, and proteins are also very important to follow prognosis and response the therapy. Recent advances in omics technologies and their use in combination can define pathophysiological pathways that can be drug targets. Biomarker discovery and their use in diagnosis in RDs is a major pillar in RD research

Two New Loci for Autosomal Recessive Ichthyosis on Chromosomes 3p21 and 19p12-q12 and Evidence for Further Genetic Heterogeneity

Autosomal recessive ichthyosis (ARI) includes a heterogeneous group of disorders of keratinization characterized by desquamation over the whole body. Two forms largely limited to the skin have been defined: lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE). A first gene for LI, transglutaminase TGM1, has been identified on chromosome 14, and a second one has been localized on chromosome 2. In a genomewide scan of nine large consanguineous families, using homozygosity mapping, two new loci for ARI were found, one for a lamellar form in a 6-cM interval on chromosome 19 and a second for an erythrodermic form in a 7.7-cM interval on chromosome 3. Linkage to one of the four loci could be demonstrated in more than half of 51 consanguineous families, most of them from the Mediterranean basin. All four loci could be excluded in the others, implying further genetic heterogeneity in this disorder. Multipoint linkage analysis gave maximal LOD scores of 11.25 at locus D19S566 and 8.53 at locus D3S3564