20.500.12556/RUL-158206 Variants in the circadian clock genes PER2 and PER3 associate with familial sleep phase disorders Delayed sleep phase disorder and advanced sleep phase disorder cause disruption of the circadian clock and present with extreme morning/evening chronotype with unclear role of the genetic etiology, especially for delayed sleep phase disorder. To assess if genotyping can aid in clinical diagnosis, we examined the presence of genetic variants in circadian clock genes previously linked to both sleep disorders in Slovenian patient cohort. Based on Morning-evening questionnaire, we found 15 patients with extreme chronotypes, 13 evening and 2 morning, and 28 controls. Sanger sequencing was used to determine the presence of carefully selected candidate SNPs in regions of the CSNK1D, PER2/3 and CRY1 genes. In a patient with an extreme morning chronotype and a family history of circadian sleep disorder we identified two heterozygous missense variants in PER3 gene, c.1243C>G (NM_001377275.1 (p.Pro415Ala)) and c.1250A>G (NM_001377275.1 (p.His417Arg)). The variants were significantly linked to Advanced sleep phase disorder and were also found in proband’s father with extreme morningness. Additionally, a rare SNP was found in PER2 gene in a patient with clinical picture of Delayed sleep phase disorder. The novel variant in PER2 (NM_022817.3):c.1901–218 G>T was found in proband’s parent with eveningness, indicating an autosomal dominant inheritance. We identified a family with autosomal dominant inheritance of two PER3 heterozygous variants that can be linked to Advanced sleep phase disorder. We revealed also a rare hereditary form of Delayed sleep phase disorder with a new PER2 variant with autosomal dominant inheritance, shedding the light into the genetic causality. circadian clock genetics PER2 sleep phase disorders genotyping PER3 true false true Angleški jezik Ni določen Članek v reviji 2024-05-29 11:09:09 2024-05-29 11:09:12 2024-08-28 12:26:53 0000-00-00 00:00:00 2024 0 0 Str. 757-766 iss. 5 Vol. 41 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.8 0742-0528 10.1080/07420528.2024.2348016 196658691 Variants_in_the_circadian_clock_genes_PER2_and_PER3_associate_with_familial_sleep_phase_disorders.pdf Variants_in_the_circadian_clock_genes_PER2_and_PER3_associate_with_familial_sleep_phase_disorders.pdf 1 EA915F3D71589B88567C2CD100B312FB ad51e7db907bfd5f43ddad00fbaac2427b41a3d089ad5460df5afa9c25a04776 990f418d-1d9b-11ef-9269-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=185715 https://www.tandfonline.com/doi/full/10.1080/07420528.2024.2348016 0 5db55e8d-1d9b-11ef-9269-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=185714 Medicinska fakulteta 0 0 0