Sadašnjost i budućnost prenatalne dijagnostike u Sloveniji

Prenatal genetic testing is under the remit of the National Health Service in Slovenia and has been included in clinical routine since the 1980s. Traditionally, prenatal services have consisted of karyotyping and rapid fetal aneuploidy screening to detect chromosome abnormalities, whereas targeted mutation testing was used for single gene disorders. Development of array comparative genomic hybridization and next generation sequencing allows for genome analysis at better resolution in a single experiment. While technological advances in medicine continue to evolve, increasing diagnostic accuracy and broadening the spectrum of indications, all these innovations require more investment along with more equipment and higher staffi ng rations trained to use it, placing burden upon healthcare funding and expenditure. This prompts us to consider how to implement new techniques into the existing services in order to update genetic services for the 21st century. Our aim is to develop a new approach to prenatal genetic services, which would maximize diagnostic yield at an acceptable cost.Prenatalno genetičko testiranje u nadležnosti je Državne zdravstvene djelatnosti u Sloveniji i uključeno je u kliničku praksu od 1980.-ih godina. Prenatalne usluge tradicionalno obuhvaćaju kariotipiziranje i brz probir na fetalne aneuploidije kako bi se otkrile kromosomne anomalije, dok se za poremećaje jednog gena provodilo ciljano testiranje na mutacije . Razvoj komparativne genomske hibridizacije na mikropostroju i sekvenciranje sljedeće generacije omogućava analizu genoma uz bolju rezoluciju u jednom testu. Dok se tehnološki napredak u medicini nastavlja poboljšavajući tako dijagnostičku točnost i šireći lepezu indikacija, ove inovacije zahtijevaju sve veća ulaganja i sve više opreme te dodatno osposobljeno osoblje koje će raditi s tom opremom, što opterećuje zdravstvene fondove i povećava troškove. To nas potiče da razmotrimo kako uklopiti nove tehnike u postojeću službu kako bismo genetičke usluge prilagodili potrebama 21. stoljeća. Cilj nam je razviti nov pristup prenatalnoj genetici kojim će se postići najučinkovitiji rezultati uz prihvatljive troškove

A critical update on endothelial nitric oxide synthase gene variations in women with idiopathic recurrent spontaneous abortion: genetic association study, systematic review and meta-analyse

A number of case–control studies investigated the association between idiopathic recurrent spontaneous abortion (IRSA) and variations in the gene encoding endothelial nitric oxide synthase (NOS3), but yielded contradictory results. Our aim was to test the association of the NOS3 variable number of tandem repeats (VNTR) in intron 4 and +894 G/T single-nucleotide polymorphism (SNP) with IRSA in Slovenian women (148 IRSA and 149 control women), conduct a systematic review of literature on the association between NOS3 gene variations and IRSA, and perform meta-analyses of studies that met the inclusion criteria, defined by virtue of the European Society for Human Reproduction and Embryology evidence-based guidelines for recurrent spontaneous abortion. Genotyping was performed using PCR and restriction fragment length polymorphism methods. The systematic review of literature (English language) was conducted using PubMed and Scopus databases, to 1 November 2014. We determined no association of IRSA with the VNTR in intron 4 and +894 G/T SNP in Slovenian women. Furthermore, 16 case–control studies were identified on the association between 15 NOS3 gene variations and IRSA. However, significant inconsistencies exist in the selection criteria of patients and controls between studies. The meta-analysis of VNTR in intron 4 was performed on five studies (894 patients, 944 controls), whereas the meta-analysis of +894 G/T SNP included six studies (1111 patients, 1121 controls). The association with IRSA was significant for the +894 G/T SNP under the dominant genetic model (GT+TT versus GG) based on fixed (odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.28–1.86, P = <0.01) and random effects models (OR = 1.54, 95% CI = 1.03–2.31, P = 0.03). In conclusion, the GT and TT genotypes of the +894 G/T SNP in women might contribute to a predisposition to IRSA. Additional genetic association and functional studies in different populations with larger numbers of participants and a uniformly defined IRSA are needed to clarify the contribution of NOS3 +894 G/T gene variation to IRSA

Y chromosome azoospermia factor region microdeletions are not associated with idiopathic recurrent spontaneous abortion in a Slovenian population: association study and literature review

Objective To investigate the potential association of Y chromosome microdeletions with idiopathic recurrent spontaneous abortion (IRSA) in a Slovenian population and compare our results with those of previously published studies in different populations, with the intention of clarifying the potential impact of Y chromosome microdeletions on IRSA. Design Case–control and association study. Setting Departments of gynecology and obstetrics and university-based research laboratory. Patient(s) Male partners of 148 couples with at least three spontaneous pregnancy losses of unknown etiology, and 148 fertile men. Intervention(s) Multiplex polymerase chain reactions. Main Outcome Measure(s) Azoospermia factor (AZF) regions were tested for Y chromosome microdeletions according to European Academy of Andrology/European Molecular Genetics Quality Network guidelines. The PubMed database was searched to retrieve articles linking Y chromosome microdeletions and susceptibility to IRSA. Result(s) None of the IRSA or control men had microdeletions in the AZFa, AZFb, or AZFc regions. A total of nine previous studies examined the relationship between Y chromosome microdeletions and IRSA, yielding contradictory results, which we discuss in detail. Conclusion(s) On the basis of our comparisons, it is unlikely that Y chromosome microdeletions contribute to IRSA and are therefore currently not recommended for the routine evaluation of IRSA couples

Leberjeva hereditarna optična nevropatija – pregled bolezni z analizo prisotnosti v Sloveniji

Leberjeva hereditarna optična nevropatija (LHON) je redka dedna mitohondrijska bolezen, ki povzroča slepoto najpogosteje pri mladih odraslih. Navadno se izrazi kot subakutna, neboleča izguba vida na eno oko, ki ji sledi poslabšanje vida drugega očesa v nekaj tednih do mesecih. Bolezen večinoma pušča trajne posledice, le pri nekaterih bolnikih lahko v redkih primerih pride do delnega spontanega izboljšanja vida. Razmerje med moškimi in ženskimi bolniki se ocenjuje na 3 : 1. V zadnjih letih je z razvojem zdravilne učinkovine idebenone možno podporno farmakološko zdravljenje, ki lahko prispeva k delnemu izboljšanju vidne funkcije. Bolezen zaradi svoje redkosti velikokrat ostane ne- ali napačno diagnosticirana. V članku predstavljamo štiri klinične primere bolnikov, pri katerih se je po obsežnem in dolgotrajnem diagnosticiranju izkazalo, da imajo LHON. Od leta 1996 se v Sloveniji vodi baza bolnikov z redkimi dednimi očesnimi boleznimi. Na tej podlagi je ocenjena prevalenca LHON 1/72.000. Ob sumu na bolezen so ključni družinska anamneza slabovidnosti po materini strani, genetsko testiranje in napotitev na obravnavo ter zdravljenje v terciarno ustanovo

UPPSÖKANDE ARBETE : En metod för studie- ochyrkesvägledare

SammanfattningAtt vissa unga varken arbetar eller studerar (UVAS) kan vara problematiskt ur olika aspekter. Till exempel ur ett samhällsperspektiv, att personen inte kan försörja sig själv och bidra till samhället. Olika professioner arbetar med arbetsmarknadsinsatser för att sysselsätta och stödja UVAS. En del personer inom denna grupp är svåra att lokalisera och komma i kontakt med, en effektiv metod för att nå ut till dem är uppsökande arbete. Syftet med denna studie var att få en djupare förståelse för hur det uppsökande arbetetser ut inom ramen för studie- och yrkesvägledarens (SYV) arbetsuppgifter i arbetet med unga i åldern 16–29 år som varken arbetar eller studerar. Resultatet från denna studie bygger på åtta stycken intervjuer med sju stycken SYV och en socionom, alla arbetar med UVAS i sin yrkesroll. Som analysverktyg för empirin användes Careershipteorin och dess centrala begrepp: handlingshorisont, brytpunkter, fält, socialt och kulturellt kapital. Resultatet visade på att UVAS är en heterogen grupp med olika förutsättningar, dock förenas många i att de har få personliga resurser. Utifråndetta är en av SYV´s främsta arbetsuppgifter att vidga målgruppens handlingshorisont genom kunskapshöjande insatser. Vidare framkom det att samverkan och uppsökande arbete är två viktiga arbetssätt för att lokalisera personer som är UVAS. Resultatet visade även på en del utmaningar i arbetet med UVAS, en strukturell utmaning är problematiken kring att inte kunna erbjuda insatser i närtid för att bibehålla motivationen hos en person som var redo att göra en förändring. Resultaten från denna studie kan bidra till att se studie- och yrkesvägledarrollen ur ett vidare perspektiv utifrånatt uppsökande arbete vanligtvis inte är en arbetsuppgift för SYV