Rare metabolic diseases in the genomics era
Аутори
Stojiljković, MajaKlaassen, Kristel
Skakić, Anita
Anđelković, Marina
Komazec, Jovana
Ugrin, Milena
Spasovski, Vesna
Pavlović, Sonja
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Introduction: All inborn metabolic diseases are rare, having a prevalence less than 1:2000. Vast majority of them are monogenic and finding pathogenic genetic variantsis needed to setthe correct diagnosis, enable adequate treatment and provide genetic counseling to members of affected family. Thisstudy is an overview of genomic studies of rare metabolic diseases in Serbia. Methods: Since 2005, more than 300 patients suspected to have a rare metabolic or neurometabolic disease have been analyzed using sanger sequencing, clinical-exome sequencing, whole-exome sequencing or whole-genome sequencing in order to find disease-causing or disease-modifying variants. Novel variants were characterized using in silico modelling or in in vitro eukaryotic assays (standard or CRISPR/Cas9 developed). Results: Disease-causing variants were found in more than 60 different genes associated with a metabolic or neurometabolic disease. The most frequent disease was phenylketonuria (109 patients), followed b...y glycogen storage disease Ib (30 patients), while majority of diseases is seen only in a single patient. More than 40 new genetic variants were comprehensively characterized in silico or in vitro. For the first time, candidate modifiers (SHANK gene family) were identified in a group of phenylketonuria patients with an unusual phenotype. Conclusion: In the genomics era, next-generation sequencing significantly shortens time to diagnosis and allowsstudying genetic modifiers of monogenic diseases and genotype-phenotype correlation. Furthermore, characterization of novel genetic targets boosts development of precision medicine
Кључне речи:
rare diseases / next-generation sequencing / genomics / precision medicineИзвор:
CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia, 2023, 36-36Издавач:
- Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Stojiljković, Maja AU - Klaassen, Kristel AU - Skakić, Anita AU - Anđelković, Marina AU - Komazec, Jovana AU - Ugrin, Milena AU - Spasovski, Vesna AU - Pavlović, Sonja PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2111 AB - Introduction: All inborn metabolic diseases are rare, having a prevalence less than 1:2000. Vast majority of them are monogenic and finding pathogenic genetic variantsis needed to setthe correct diagnosis, enable adequate treatment and provide genetic counseling to members of affected family. Thisstudy is an overview of genomic studies of rare metabolic diseases in Serbia. Methods: Since 2005, more than 300 patients suspected to have a rare metabolic or neurometabolic disease have been analyzed using sanger sequencing, clinical-exome sequencing, whole-exome sequencing or whole-genome sequencing in order to find disease-causing or disease-modifying variants. Novel variants were characterized using in silico modelling or in in vitro eukaryotic assays (standard or CRISPR/Cas9 developed). Results: Disease-causing variants were found in more than 60 different genes associated with a metabolic or neurometabolic disease. The most frequent disease was phenylketonuria (109 patients), followed by glycogen storage disease Ib (30 patients), while majority of diseases is seen only in a single patient. More than 40 new genetic variants were comprehensively characterized in silico or in vitro. For the first time, candidate modifiers (SHANK gene family) were identified in a group of phenylketonuria patients with an unusual phenotype. Conclusion: In the genomics era, next-generation sequencing significantly shortens time to diagnosis and allowsstudying genetic modifiers of monogenic diseases and genotype-phenotype correlation. Furthermore, characterization of novel genetic targets boosts development of precision medicine PB - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade C3 - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia T1 - Rare metabolic diseases in the genomics era EP - 36 SP - 36 UR - https://hdl.handle.net/21.15107/rcub_imagine_2111 ER -
@conference{ author = "Stojiljković, Maja and Klaassen, Kristel and Skakić, Anita and Anđelković, Marina and Komazec, Jovana and Ugrin, Milena and Spasovski, Vesna and Pavlović, Sonja", year = "2023", abstract = "Introduction: All inborn metabolic diseases are rare, having a prevalence less than 1:2000. Vast majority of them are monogenic and finding pathogenic genetic variantsis needed to setthe correct diagnosis, enable adequate treatment and provide genetic counseling to members of affected family. Thisstudy is an overview of genomic studies of rare metabolic diseases in Serbia. Methods: Since 2005, more than 300 patients suspected to have a rare metabolic or neurometabolic disease have been analyzed using sanger sequencing, clinical-exome sequencing, whole-exome sequencing or whole-genome sequencing in order to find disease-causing or disease-modifying variants. Novel variants were characterized using in silico modelling or in in vitro eukaryotic assays (standard or CRISPR/Cas9 developed). Results: Disease-causing variants were found in more than 60 different genes associated with a metabolic or neurometabolic disease. The most frequent disease was phenylketonuria (109 patients), followed by glycogen storage disease Ib (30 patients), while majority of diseases is seen only in a single patient. More than 40 new genetic variants were comprehensively characterized in silico or in vitro. For the first time, candidate modifiers (SHANK gene family) were identified in a group of phenylketonuria patients with an unusual phenotype. Conclusion: In the genomics era, next-generation sequencing significantly shortens time to diagnosis and allowsstudying genetic modifiers of monogenic diseases and genotype-phenotype correlation. Furthermore, characterization of novel genetic targets boosts development of precision medicine", publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade", journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia", title = "Rare metabolic diseases in the genomics era", pages = "36-36", url = "https://hdl.handle.net/21.15107/rcub_imagine_2111" }
Stojiljković, M., Klaassen, K., Skakić, A., Anđelković, M., Komazec, J., Ugrin, M., Spasovski, V.,& Pavlović, S.. (2023). Rare metabolic diseases in the genomics era. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 36-36. https://hdl.handle.net/21.15107/rcub_imagine_2111
Stojiljković M, Klaassen K, Skakić A, Anđelković M, Komazec J, Ugrin M, Spasovski V, Pavlović S. Rare metabolic diseases in the genomics era. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:36-36. https://hdl.handle.net/21.15107/rcub_imagine_2111 .
Stojiljković, Maja, Klaassen, Kristel, Skakić, Anita, Anđelković, Marina, Komazec, Jovana, Ugrin, Milena, Spasovski, Vesna, Pavlović, Sonja, "Rare metabolic diseases in the genomics era" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):36-36, https://hdl.handle.net/21.15107/rcub_imagine_2111 .