Pregledni rad
https://doi.org/10.26800/LV-145-supl1-36
Genomic diagnostic algorithms in families with neurodevelopmental disorders
Feodora Stipoljev
; Odjel za laboratorijsku citogenetiku, Klinika za ginekologiju i porodništvo, Klinička bolnica “Sveti Duh”, Zagreb
Maja Oroz
Ana Vičić
Sažetak
Genetic testing in patients with neurodevelopmental disorders is very important for making a final diagnosis. According to the current guidelines, the first line methods include Microarray-based Comparative Genomic Hybridization and genetic testing of Fragile X Syndrome. Whole-exome sequencing, which allows detection of single-nucleotide variants in the coding regions of genes, represents the next diagnostic step. The diagnostic yield of Comparative Genomic Hybridization is up to 15%, while for whole-exome sequencing it
increases up to 40%. However, in a large number of patients (up to 50%), the etiology of neurodevelopmental disorders remains unexplained. Even though there are many familiar genetic mechanisms, some of them cannot be established by routine diagnostic methods, such as copy number variants in non-coding regulatory DNA regions, copy number variants that affect structure and function of topologically associating domains (TADs), deep intronic variants in coding genes as well as genome-wide methylation patterns. The aforementioned genetic changes can be detected with newer technologies such as whole-genome sequencing and mapping of TADs
(Hi-C sequencing). With whole-genome sequencing it is possible to determine precise breakpoints in apparently balanced chromosomal arrangements. Therefore introduction of whole-genome sequencing in the routine diagnostics of genetic diseases would certainly increase the diagnostic yield and enable setting up diagnosis for a large number of patients with neurodevelopmental disorders. With the advancement of technology and the increasing availability of whole-genome sequencing, a rise in the amount of available data in genomic databases is expected in the near future. This would allow the interpretation of the large amount of data generated by this method and accelerate the introduction of this powerful method into routine medical care for patients with genetic disorders.
Ključne riječi
NEURODEVELOPMENTAL DISORDERS; ACGH; WHOLE EXOME SEQUENCING; WHOLE GENOME SEQUENCING
Hrčak ID:
300863
URI
Datum izdavanja:
17.4.2023.
Posjeta: 539 *