Vilnius University, Department of Human and Medical Genetics, Vilnius, Lithuania
Background. Intellectual disability affects about 1–2% of the general popula¬tion worldwide, and this is the leading socio-economic problem of health care. The evaluation of the genetic causes of intellectual disability is challenging be¬cause these conditions are genetically heterogeneous with many different ge¬netic alterations resulting in clinically indistinguishable phenotypes. Genome wide molecular technologies are effective in a research setting for establishing the new genetic basis of a disease. The first Lithuanian experience in genome-wide CNV detection and whole exome sequencing gained during UNIGENE project will be presented.
Results. More than 100 patients with unknown etiology of intellectual disability were enrolled in the UNIGENE project. New technologies allowed to establish the genetic diagnosis in ~20% of the patients. Few rare pathogenic variants causing intellectual disability using high throughput NGS technique have been discovered. New phenotypic observations of recognizable syndromes added new insights for further delineation of the known disorders. Clinical characterization of the patients with novel pathogenic variants expanded the clinical spectrum of syndromes.
Conclusions. The genetic heterogeneity of intellectual disability requires genome wide approaches, including detection of chromosomal aberrations by chromosomal microarrays and whole exome sequencing capable of un¬covering single gene pathogenic variants. This study demonstrates the benefits and challenges that accompany the use of genome wide molecular technologies and provides genotype-phenotype information on patients with rare genetic alterations.