209 research outputs found

    Preface

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    Case report: State-of-the-art risk-modifying treatment of sudden cardiac death in an asymptomatic patient with a mutation in the SCN5A gene and a review of the literature

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    Brugada syndrome is a rare hereditary disorder characterized by distinct ECG findings, complex genetics, and a high risk of sudden cardiac death. Recognition of the syndrome is crucial as it represents a paradigm of sudden death tragedy in individuals at the peak of their lives. Notably, Brugada syndrome accounts for more than 20% of sudden cardiac deaths in individuals with structurally normal hearts. Although this syndrome follows an autosomal dominant inheritance pattern, it is more prevalent and severe in males. Diagnosis is primarily based on the characteristic ECG pattern observed in the right precordial leads. Mutations in the SCN5A gene, resulting in loss of function, are the most common genetic cause. We presented a 36-year-old proband with a family history of sudden cardiac death. Although the patient was asymptomatic for Brugada syndrome, his father had experienced sudden death at the age of 36. The proband was admitted to St. Catherine's Specialty Hospital where blood was taken and subjected to next-generation sequencing (NGS) using a ā€œSudden cardiac deathā€ panel. The analysis identified a pathogenic variant in the SCN5A gene [c.4222Gā€‰>ā€‰A(p.Gly1408Arg)], which is associated with autosomal dominant Brugada syndrome. Based on the positive genetic test result, the patient was referred for further examination. ECG with modified precordial lead positioning confirmed the presence of the Brugada phenotype, displaying the type-2 and type-1 ECG patterns. Therefore, we made the diagnosis and decided to implant an implantable cardioverter-defibrillator (ICD) based on the results of broad genetic NGS testing, diagnostic criteria (ECG), and considering the high burden of sudden cardiac death in the patient's family, as well as his concerns that limited his everyday activities. This case shows that genetics and personalized medicine hold immense potential in the primary prevention, diagnosis, and treatment of Brugada syndrome and sudden cardiac death

    Analiza DNA u sudskoj medicini i njezina primjena u hrvatskome kaznenopravnom sustavu

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    U izlaganju se daje kratak pregled tijeka razvoja istraživanja DNA kao ā€œnovog znanstvenog dokazaā€ odnosno odgovora znanosti na sve profesionalniji pristup počinitelja u planiranju počinjenja te prikrivanju tragova kaznenog djela i potrebu očuvanja najvažnijih vrijednosti svake pravne države. Posebno se iznose novine vezane uz DNA analizu bioloÅ”kih materijala i DNA baze podataka kroz novi Zakon o kaznenom postupku. Također, izlaganje prikazuje nastojanje da se prvi put u hrvatskome kaznenopravnom sustavu omogući izuzimanje bioloÅ”kog materijala, radi provođenja DNA analize, od pravomoćno osuđenih osoba koje se nalaze na izdržavanju kazne zatvora, i to kroz predložene izmjene Zakona o izvrÅ”avanju kazne zatvora, koje su trenutno u saborskoj proceduri

    Twelfth ISABS Conference on Forensic and Anthropologic Genetics and Mayo Clinic Lectures in Individualized Medicine, Dubrovnik, Croatia, June 22-27, 2022

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    Welcome to the twelfth ISABS conference on forensic and anthropological genetics and Mayo clinic lectures in individualized medicine!

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    We invite you to join us at the 12th ISABS Conference on Forensic, Anthropological and Medical Genetics, Dubrovnik, Croatia, June 22 ā€“ 27, 2022. The conference is the next in the series of biennial events organized by the International Society for Applied Biological Sciences (ISABS), a society dedicated to the promotion of applied molecular biology (www.isabs.net)

    The impact of COVID-19 on sustainable development

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    Osteogenesis imperfecta: klinička procjena i liječenje

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    Osteogenesis imperfecta (OI) is a phenotypically and molecularly heterogeneous group of heritable connective tissue disorders characterized by low bone mineral density, recurrent fractures, and bone deformities. Most cases of OI are inherited in an autosomal dominant manner and are caused by mutations in the COL1A1 and COL1A2 genes, leading to quantitative or qualitative defects in type 1 collagen. More recently, a number of other genes responsible for both recessive and dominant forms of this condition have been identifi ed. In this brief review, we discuss current understanding of clinical assessment, follow-up and pharmacological therapies for the treatment of OI. The multidisciplinary surveillance in patients with OI includes periodical hearing and vision testing, dental examination, spirometry or body plethysmography, evaluation of heart/valvular function, and neurological and psychological assessment. There is a need for regular assessment of bone mineral density (BMD) to evaluate treatment success and disease progression, and skeletal radiographs at the time of diagnosis and later as indicated by orthopaedists. Treatment of OI is aimed at preventing or controlling the symptoms present in individual patient with the main goals to decrease fracture rate, relieve bone pain, and provide suffi cient bone mass and good muscle strength promoting self-mobility and growth. This requires a multi-disciplinary approach, utilizing medical treatment, physical therapy, orthopedic surgery, and nutrition monitoring. Intravenous bisphosphonate therapy is the most widely used medical treatment. It has an evident eff ect on BMD of lumbar spine, femoral neck and total hip in growing children and can lead to vertebral reshaping after compression fractures, but no signifi cant eff ect on the risk of fractures has been observed in adults. Other novel promising therapies include teriparatide, combination therapy with antiresorptive and anabolic drugs, denosumab, transforming growth factor beta, sclerostin and cathepsin K inhibitors, and cell-based therapy, such as bone marrow or mesenchymal stem cell transplantation. Gene targeting approaches are still at early stages of investigation.Osteogenesis imperfecta (OI) je fenotipski i molekularno heterogena skupina nasljednih bolesti veziva obilježena smanjenom gustoćom kostiju, čestim lomovima i deformacijama. Većina OI-a nasljeđuje se autosomno dominantno i uzrokovana je mutacijama u genima COL1A1 i COL1A2, Å”to dovodi do kvantitativnog ili kvalitativnog defekta kolagena tip 1. U posljednje vrijeme otkriven je veći broj gena koji su odgovorni za recesivne i dominantne oblike ove bolesti. U ovom kratkom pregledu razmatramo suvremeni pristup kliničkoj dijagnostici i praćenju te farmakoloÅ”kom liječenju OI-a. Multidisciplinsko praćenje bolesnika uključuje povremeno testiranje sluha i vida, stomatoloÅ”ke preglede, spirometriju ili pletizmografi ju, evaluaciju funkcije srca/valvula, neuroloÅ”ke i psiholoÅ”ke kontrole. Potrebno je redovito pratiti vrijednosti gustoće kostiju (BMD) kako bi se utvrdio uspjeh liječenja i progresija bolesti, a nužne su i rengenske slike kostiju kod postavljanja dijagnoze i kasnije prema indikaciji ortopeda. Svrha liječenja je i da spriječi ili suzbije simptome prisutne kod pojedinog bolesnika, a glavni ciljevi su smanjiti broj lomova, suzbiti bol, poboljÅ”ati koÅ”tanu masu i miÅ”ićnu snagu te osigurati samostalnu pokretnost i rast. To zahtijeva multidisciplinski pristup u liječenju lijekovima, fi zikalnom terapijom, kiruÅ”kim ortopedskim zahvatima i odgovarajućom prehranom. Intravenska primjena bisfosfonata je najÅ”ire primjenjivan oblik medikamentoznog liječenja. Ona ima očit učinak na BMD slabinske kralježnice, vrata bedrene kosti i kukova djece u rastu, te može dovesti do preoblikovanja kralježaka nakon kompresijskih fraktura, ali nema značajnijeg učinka na rizik pojave lomova kod odraslih osoba. Druge nove obećavajuće terapije uključuju teriparatid, liječenje kombinacijom antiresorptivnih i anaboličih lijekova, denosumab, inhibiciju TGF-Ī² (eng. transforming growth factor beta), sklerostina i kathepsina K te staničnu terapiju, poput transplantacije koÅ”tane srži ili mezenimalnih stanica. Genska terapija je joÅ” u ranim stadijima ispitivanja

    Molekularno-genetička analiza osteogenesis imperfecta u kliničkoj praksi

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    Osteogenesis imperfecta (OI) is characterized by fractures with minimal or absent trauma, representing a continuum ranging from perinatal lethality through individuals with severe skeletal deformities to nearly asymptomatic individuals with mild predisposition to fractures. Diagnosis of OI is an interdisciplinary task based on family and/or patient history of fractures combined with characteristic physical fi ndings. Radiographic examination reveals fractures of varying ages and stages of healing, wormian bones, and osteopenia. As there is no defi nitive test for OI, molecular genetic testing by next generation sequencing (NGS) of COL1A1 and COL1A2 and up to 12 other genes is essential to confi rm the genetic background. Therefore, we designed a NGS gene panel comprising 12 genes involved in OI or severe osteoporosis. Here we report results in a cohort of 11 apparently sporadic young patients with OI, all off spring of unaff ected parents, who were referred to orthopaedic surgery at Sv. Katarina Special Hospital (Zabok/Zagreb, Croatia). Ten of these 11 patients could be classifi ed genetically. Overall, three genes with diff erent percent relating to the whole cohort were involved: COL1A1 (63.6%), COL1A2 (18.18%) and WNT1 (9.09%).Osteogenesis imperfecta (OI) je obilježena prijelomima uz minimalnu ili odsutnu traumu i predstavlja kontinuum u rasponu od perinatalne smrtnosti, osobe s teÅ”kim skeletnim deformitetima do gotovo asimptomatskih osoba s niskom sklonoŔću prijelomima. Dijagnosticiranje OI je interdisciplinski zadatak koji se temelji na obiteljskoj i/ili bolesnikovoj povijesti prijeloma u kombinaciji sa znakovitim fi zičkim nalazima. Radiografsko snimanje otkriva prijelome različite starosti i stadija zaraÅ”tanja, Wormove kosti i osteopeniju. Kako nema konačnog testa za OI, molekularno genetsko testiranje pomoću next generation sequencing (NGS) gena COL1A1 i COL1A2 te do 12 drugih gena bitno je za potvrdu genetske podloge. Stoga smo izradili NGS genski panel koji sadrži 12 gena uključenih u OI ili teÅ”ku osteoporozu. Prikazujemo rezultate dobivene u nizu od 11 očito sporadičnih mladih bolesnika s OI, svi potomci nezahvaćenih roditelja, koji su bili upućeni na ortopedsku kirurgiju u Specijalnoj bolnici sv. Katarina u Zaboku/Zagrebu. Deset od tih 11 bolesnika mogli smo genetski klasifi cirati. Sveukupno, uključena su bila tri gena u različitim postocima u naÅ”em nizu bolesnika: COL1A1 (63,6%), COL1A2 (18,18%) i WNT1 (9,09%)
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