209 research outputs found
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
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 āSudden cardiac deathā panel. The analysis identified a pathogenic variant in the SCN5A gene [c.4222Gā>āA(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
U izlaganju se daje kratak pregled tijeka razvoja istraživanja DNA
kao ānovog znanstvenog dokazaā odnosno odgovora znanosti na sve
profesionalniji pristup poÄinitelja u planiranju poÄinjenja te prikrivanju
tragova kaznenog djela i potrebu oÄuvanja najvažnijih vrijednosti
svake pravne države. Posebno se iznose novine vezane uz DNA
analizu bioloŔkih materijala i DNA baze podataka kroz novi Zakon
o kaznenom postupku. TakoÄer, izlaganje prikazuje nastojanje da se
prvi put u hrvatskome kaznenopravnom sustavu omoguÄi izuzimanje
bioloÅ”kog materijala, radi provoÄenja DNA analize, od pravomoÄno
osuÄenih osoba koje se nalaze na izdržavanju kazne zatvora, i to kroz
predložene izmjene Zakona o izvrŔavanju 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
Welcome to the twelfth ISABS conference on forensic and anthropological genetics and Mayo clinic lectures in individualized medicine!
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)
Osteogenesis imperfecta: kliniÄka procjena i lijeÄenje
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 gustoÄom
kostiju, Äestim lomovima i deformacijama. VeÄina OI-a nasljeÄuje 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 veÄi
broj gena koji su odgovorni za recesivne i dominantne oblike ove bolesti. U ovom kratkom pregledu razmatramo suvremeni pristup
kliniÄkoj dijagnostici i praÄenju te farmakoloÅ”kom lijeÄenju OI-a. Multidisciplinsko praÄenje bolesnika ukljuÄuje povremeno testiranje
sluha i vida, stomatoloŔke preglede, spirometriju ili pletizmografi ju, evaluaciju funkcije srca/valvula, neuroloŔke i psiholoŔke kontrole.
Potrebno je redovito pratiti vrijednosti gustoÄe kostiju (BMD) kako bi se utvrdio uspjeh lijeÄenja i progresija bolesti, a nužne su i
rengenske slike kostiju kod postavljanja dijagnoze i kasnije prema indikaciji ortopeda.
Svrha lijeÄenja je i da sprijeÄi ili suzbije simptome prisutne kod pojedinog bolesnika, a glavni ciljevi su smanjiti broj lomova, suzbiti
bol, poboljÅ”ati koÅ”tanu masu i miÅ”iÄnu snagu te osigurati samostalnu pokretnost i rast. To zahtijeva multidisciplinski pristup u lijeÄenju
lijekovima, fi zikalnom terapijom, kiruÅ”kim ortopedskim zahvatima i odgovarajuÄom prehranom. Intravenska primjena bisfosfonata
je najÅ”ire primjenjivan oblik medikamentoznog lijeÄenja. Ona ima oÄit uÄinak na BMD slabinske kralježnice, vrata bedrene kosti
i kukova djece u rastu, te može dovesti do preoblikovanja kralježaka nakon kompresijskih fraktura, ali nema znaÄajnijeg uÄinka na
rizik pojave lomova kod odraslih osoba. Druge nove obeÄavajuÄe terapije ukljuÄuju teriparatid, lijeÄenje kombinacijom antiresorptivnih
i anaboliÄih lijekova, denosumab, inhibiciju TGF-Ī² (eng. transforming growth factor beta), sklerostina i kathepsina K te staniÄnu
terapiju, poput transplantacije koŔtane srži ili mezenimalnih stanica. Genska terapija je joŔ u ranim stadijima ispitivanja
Molekularno-genetiÄka analiza osteogenesis imperfecta u kliniÄkoj praksi
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 sklonoÅ”Äu prijelomima.
Dijagnosticiranje OI je interdisciplinski zadatak koji se temelji na obiteljskoj i/ili bolesnikovoj povijesti prijeloma u kombinaciji sa
znakovitim fi ziÄkim nalazima. Radiografsko snimanje otkriva prijelome razliÄite starosti i stadija zaraÅ”tanja, Wormove kosti i osteopeniju.
Kako nema konaÄnog testa za OI, molekularno genetsko testiranje pomoÄu 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 ukljuÄenih
u OI ili teÅ”ku osteoporozu. Prikazujemo rezultate dobivene u nizu od 11 oÄito sporadiÄnih mladih bolesnika s OI, svi potomci
nezahvaÄenih roditelja, koji su bili upuÄeni na ortopedsku kirurgiju u Specijalnoj bolnici sv. Katarina u Zaboku/Zagrebu. Deset od tih
11 bolesnika mogli smo genetski klasifi cirati. Sveukupno, ukljuÄena su bila tri gena u razliÄitim postocima u naÅ”em nizu bolesnika:
COL1A1 (63,6%), COL1A2 (18,18%) i WNT1 (9,09%)
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