Recent advances in genetics are opening new possibilities for faster and more effective diagnostics of rare genetic disorders, which due to their diversity as well as genetic and phenotypic heterogeneity, commonly represent a significant diagnostic challenge.
The new methodologies, especially clinical exome sequencing (CES), whole human exome (WES) and genome sequencing (WGS), now allow comprehensive and complete analysis of genetic variation in a patient with suspected or undefined genetic diagnosis. To ensure the efficient and active translation of rising into clinical practice, we have established a Centre for Mendelian genomics (CMG) at the Clinical Institute of Medical Genetics in Ljubljana in 2013. Since the establishment, we have performed whole exome and clinical exome sequencing in over 2000 cases affected by a wide variety of suspected genetic disorders, including neurological, cardiovascular, developmental and various other conditions.
Depending on the disease class, we were able to identify genetic cause in 40% to 80% of patients with suspected rare disorders, depending on the diagnosis of referral.
To maximize the diagnostic yield, we have implemented a custom analytic pipeline for identification of potentially causative single nucleotide variants, copy number variants and mitochondrial variation. Furthermore, we have developed an effective variant prioritization approach that combines pathogenicity properties of variants, information on known modes of inheritance and phenotypic associations of genes carrying the variants.
Our mission is to translate new genomic technologies in diagnostics of patients with rare genetic disorders and present the benefits stemming from establishment of regional centre for diagnostic evaluation of patients with rare diseases.
– Next-generation sequencing
Time to reporting
– 3-6 months depending on the complexity
– Urgent clinical exome sequencing is performed in selected cases with the expected first information in the period of 3-4 weeks