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Medicinska genetika je medicinska specijalizacija u kojoj se primjenjuju principi i znanja o nasljeđivanju u prepoznavanju, dijagnostici, prevenciji i liječenju bolesti te unaprjeđivanju zdravlja. Uloga medicinskog genetičara je organizacija skrbi za pacijente s genetičkim poremećajima, što uključuje prepoznavanje indikacija za genetičko testiranje, provođenje genetičkog testiranja i organizaciju cjeloživotne skrbi. S obzirom na to da je medicinska genetika izuzetno multidisciplinarna specijalizacija, medicinski genetičari koordiniraju skrb za pacijenta s drugim specijalistima, logopedima, psiholozima, udrugama pacijenata. Medicinska genetika i logopedija izrazito su isprepletene brojnim poveznicama, od činjenice da je ljudska vrsta jedinstvena po postojanju jezika, koji je barem djelomično genetički kodiran, do toga da su pacijenti s genetičkim uzrocima razvojnih govorno-jezičnih poremećaja neizbježno uključeni u zajedničku skrb obiju vrsti stručnjaka. Stoga je izuzetno važno osvijestiti ulogu logopeda u području medicinske genetike, koja uključuje, s jedne strane, povezivanje nalaza genetičkog testiranja s očekivanim kliničkim obilježjima i ispravnim pristupom pacijentu s potvrđenim genetičkim uzrokom razvojnog govorno-jezičnog poremećaja te, s druge strane, prepoznavanje pacijenata s mogućim genetičkim uzrokom razvojnog govorno-jezičnog poremećaja. Priručnik Osnove medicinske genetike za studente logopedije obvezna je literatura za obvezni kolegij Osnove medicinske genetike na drugoj godini studija Logopedija. Osnovni su ciljevi priručnika i kolegija opisati i objasniti (1) osnovne pojmove iz genetike čovjeka potrebne za razumijevanje nastajanja i nasljeđivanja genetičkih poremećaja, (2) genetičke uzroke razvojnih govorno-jezičnih poremećaja te (3) osnove interpretacije nalaza genetičkog testiranja u kontekstu povezivanja s očekivanim kliničkim obilježjima i ispravnim pristupom pacijentu s razvojnim govorno-jezičnim poremećajem. Ovaj priručnik nastao je kao odgovor na nekoliko činjeničnih stanja u području medicinske genetike u svijetu, posebice u njezinu spoju s logopedijom. Prije svega, osnovna vizija i ideja za čitav kolegij bila je da se, s ciljem stjecanja specifičnih znanja, vještina i vrijednosti/stavova, svi oblici nastave (predavanja, seminari i vježbe) provode kroz metode aktivnog učenja temeljene na problemskom i iskustvenom učenju, potičući razvijanje otvorenog, analitičkog i kritičkog razmišljanja. Ovakvim pristupom učenju i poučavanju, obrnutnim od klasičnog načina, potiče se jednostavnije i svrhovitije savladavanje i primjena osnovnih teorijskih znanja, kao i razmišljanje o pacijentu u obrascima kliničkih obilježja. Nadalje, u postojećoj literaturi trenutno nema sličnih nastavnih priručnika koji bi omogućili učenje medicinske genetike u području logopedije, pa je navedeni koncept aktivnog učenja ključan za simulaciju stvarnog oblika djelovanja u kliničkoj praksi. U priručniku se nalaze brojni zadatci za savladavanje različitih razina znanja (kognitivna domena), vještina (psihomotorna domena) i vrijednosti i stavova (afektivna domena). Zadatci omogućavaju timski ili samostalni rad, vođenu argumentiranu raspravu i istraživanje rješenja problema, što osim postavljenih ishoda učenja za kolegij omogućava razvijanje i općih kompetencija, poput znanja i vještina za praksu te osjećaj samostalnosti i uvažavanja kolega. Naposljetku, s obzirom na to da je medicinska genetika jedna od najbrže razvijajućih medicinskih specijalizacija, pa većina gradiva u udžbenicima zastarijeva već prilikom njihova izdavanja, ovaj priručnik omogućava brzu prilagodbu i nadopunjavanje najnovijim spoznajama kroz jednostavne promjene sadržaja. Nastavnici polaznike tijekom nastave cijelo vrijeme strukturirano vode kroz priručnik na predavanjima, seminarima i vježbama. Predavanja, seminari i vježbe su u priručniku označeni različitim bojama naslova, što uvelike pridonosi brzom snalaženju i preglednosti. U prvom dijelu priručnika i nastave, gradivo je posvećeno osnovama genetike čovjeka, a drugi dio osnovama medicinske genetike, uz posebnu pažnju usmjerenu na analizu slučajeva. Primjeri genetičkih bolesti i poremećaja koji su prikazani u priručniku isključivo su oni s kojima se logopedi najčešće susreću po završenom studiju. Naposljetku, tijekom kolegija Osnove medicinske genetike poseban je naglasak stavljen na razvijanje afektivne domene, jer je ključno da, osim navedenih specifičnih znanja i vještina, budući logopedi razviju osviještenost za multidimenzionalnost genetičkih bolesti i poremećaja, kao i važnosti djelovanja u multidisciplinarnom timu, za dobrobit pacijenata s razvojnim govorno-jezičnim poremećajima.

Introduction Heterozygous pathogenic and likely pathogenic sequence variants in the RUNX1 (Runt-related Transcription Factor 1) gene are a common genetic cause of decreased platelet count and/or platelet dysfunction and an increased risk of developing myelodysplasia and acute myeloid leukemia. The majority of causative variants are substitutions, which rarely occur de novo. The aim of this case report is to present a patient with congenital thrombocytopenia caused by a deletion variant in exon 9 in the RUNX1 gene. Case report A one-month-old male infant was admitted to the Clinical Hospital Center Rijeka because of anemia and thrombocytopenia verified in the course of an acute viral infection. During follow-up, he occasionally had petechiae and ecchymoses on the lower extremities after mild trauma, with no other symptoms. The patient had persistent slightly decreased values of platelets with normal morphology, but with pathological aggregation with adrenaline and adenosine diphosphate. Due to the unclear etiology of persistent mild thrombocytopenia, he was referred for genetic testing at the age of five. Genomic DNA was isolated from the patient’s peripheral blood and whole-exome sequencing was performed using the next-generation sequencing method. A heterozygous frameshift variant, c.1160delG (NM_001754.4), was identified in exon 9. The variant is classified as likely pathogenic. Conclusion To the best of our knowledge, the heterozygous variant c.1160delG in the RUNX1 gene was first described in our patient. Although pathogenic variants in the RUNX1 genes are very rare, persistently low platelet counts of unclear etiology should raise suspicion of an underlying genetic disorder.

To examine the knowledge, behavior, and attitudes toward medical genetics among obstetrics and gynecology, pediatrics, and neurology residents and specialists. The cross-sectional study involved 182 non-genetic residents and specialists in the Republic of Croatia, who completed a validated online questionnaire anonymously and voluntarily. The questionnaire consisted of five groups of questions: general information, knowledge, behavior in practice, attitude toward genetic testing, and additional education in medical genetics. The median score for overall knowledge of medical genetics was 70.2% among obstetrician- gynecologists, 80.5% among pediatricians, and 76.7% among neurologists (P

BRCA1 i BRCA2 geni najčešći su uzrok nasljednog raka dojke i jajnika te igraju ključnu ulogu u održavanju stabilnosti genoma i popravaku oštećene DNA. Mutacije u genima BRCA1 i BRCA2 mogu poremetiti normalno funkcioniranje ovih proteina, što dovodi do povećanog rizika od razvoja raka dojke i jajnika. Pojedinci s pozitivnom obiteljskom anamnezom ovih vrsta karcinoma ili oni koji nose poznate patogene varijante sekvence u tim genima imaju indikaciju za genetičko testiranje. Razni multigenski paneli mogu identificirati mutacije u BRCA1 i BRCA2, pomažući u procjeni rizika i informirajući o odlukama u liječenju. Pojedincima kojima je identificirana patogena varijanta u BRCA1 ili BRCA2 genima, mogu se implementirati personalizirane strategije liječenja. Kirurgija igra ključnu ulogu u liječenju BRCA1 i BRCA2 karcinoma dojke i jajnika dok je kemoterapija na bazi platine često izbor prve linije adjuvantnog i neoadjuvantnog liječenja. Dodatni lijekovi za kemoterapiju, kao što su taksani, mogu se kombinirati s platinastim lijekovima kako bi se poboljšali ishodi liječenja, a ciljane terapije, posebno PARP inhibitori, iskorištavaju defekte popravka DNK uzrokovane BRCA mutacijama, dovodeći do selektivnog ubijanja stanica raka. Cilj ovog rada je pružiti sveobuhvatno objašnjenje u vezi s prirodom gena BRCA1 i BRCA2, razjašnjavajući mehanizme koji stoje iza njihove mutacije te navesti kontrastne karakteristike nasljednih i sporadičnih varijanti povezanih karcinoma., BRCA1 and BRCA2 genes are known for their association with hereditary breast and ovarian cancer. These genes play a key role in maintaining genome stability and are involved in the repair of damaged DNA. Mutations in the BRCA1 and BRCA2 genes can disrupt the normal functioning of these proteins, leading to an increased risk of developing breast and ovarian cancer. Individuals with a family history of these types of cancer or those who carry known pathogenic variants in these genes may benefit from genetic testing. A variety of multigene panels can identify mutations in BRCA1 and BRCA2, helping to assess risk and inform treatment decisions. For individuals identified as carriers of pathogenic BRCA1 or BRCA2 variants, personalized treatment strategies can be implemented. Surgery plays a key role in the treatment of BRCA1 and BRCA2 breast and ovarian cancers, while platinum-based chemotherapy is often the first-line choice of adjuvant and neoadjuvant treatment. Additional chemotherapy drugs, such as taxanes, can be combined with platinum drugs to improve treatment outcomes, and targeted therapies, particularly PARP inhibitors, exploit DNA repair defects caused by BRCA mutations, leading to selective killing of cancer cells. The aim of this paper is to provide a comprehensive explanation regarding the nature of the BRCA1 and BRCA2 genes, elucidating the mechanisms behind their mutation and to state the contrasting characteristics of hereditary and sporadic variants of related cancers.

Muška neplodnost prevladavajući je reproduktivni poremećaj koji pogađa značajan dio parova diljem svijeta. Iako različiti čimbenici doprinose muškoj neplodnosti, nedavna su istraživanja rasvijetlila ključnu ulogu genetike u ovom stanju. Ovaj diplomski rad pruža opsežan pregled genetičkih čimbenika povezanih s muškom neplodnošću, istražujući i kromosomske aberacije i specifične genske mutacije koje utječu na plodnost muškaraca. Razumijevanje genetičke podloge muške neplodnosti ključno je za razvoj učinkovitih dijagnostičkih alata, personaliziranih tretmana i strategija genetičkog savjetovanja. Kromosomske aberacije igraju značajnu ulogu u muškoj neplodnosti, sa širokim rasponom strukturnih i numeričkih aberacija, kao što su Klinefelter sindrom (47,XXY), mikrodelecije Y kromosoma i balansirane aberacije. Nadalje, nekoliko pojedinačnih genskih mutacija identificirane su kao čimbenici koji pridonose muškoj neplodnosti, uključujući CFTR gen (regulator transmembranske provodljivosti cistične fibroze), koji je povezan s kongenitalnom bilateralnom odsutnošću sjemenovoda, i AR gen (androgeni receptor), povezan sa sindromom neosjetljivosti na androgene. Kallmannov sindrom također je posljedica genetičke promjene u DNA, a manifestira se kao prirođeni oblik hipogonadotropnog hipogonadizma., Male infertility is a prevalent reproductive disorder that affects a significant proportion of couples worldwide. Although various factors contribute to male infertility, recent research has shed light on the key role genetics play in this condition. This thesis provides a comprehensive summary of the genetic factors associated with male infertility, exploring both chromosomal abnormalities and specific gene mutations that affect male fertility. Understanding the genetic basis of male infertility is critical to the development of effective diagnostic tools, personalized treatments, and genetic counseling strategies. Chromosomal abnormalities play a significant role in male infertility, with a wide range of structural and numerical anomalies implicated. This section discusses common chromosomal abnormalities, such as Klinefelter syndrome (47,XXY), Y chromosome microdeletions, and reciprocal translocations. It emphasizes their influence on spermatogenesis, hormonal imbalance and overall fertility. Several individual gene mutations have been identified as contributing factors to male infertility. This section focuses on genes associated with spermatogenesis, including the CFTR gene (cystic fibrosis transmembrane conductance regulator), which is associated with congenital bilateral absence of the vas deferens (CBAVD), and the AR gene (androgen receptor), associated with androgen insensitivity syndrome (AIS). Kallmann's syndrome is also the result of a genetic change in DNA, and manifests itself as a congenital form of hypogonadotropic hypogonadism.

Uniparentna disomija (UPD) je stanje u kojem homologni par kromosoma u cijelosti ili samo djelomično potječu od jednog roditelja. Dalje se UPD-ovi dijele na izodisomije i heterodisomije. UPD-om se mogu prenijeti autosomno recesivne (AR) bolesti čak i ako je samo jedan roditelj nosioc te ako se radi o UPD-u kromosoma 6, 7, 11, 14, 15 ili 20, mogu nastati određeni sindromi koji su posljedica poremećaja genomskog upisa. Genomski upis je epigenetički mehanizam koji dopušta ekspresiju određenih gena ovisno o roditeljskom podrijetlu. Poremećaj genomskog upisa stvara disbalans među upisanim genima koji je posljedica pretjerane aktivacije ili pretjerane inaktivacije određenih gena. Na taj način nastaju sindromi UPD-ova. Prader-Willi sindrom (PWS) i Angelman sindrom (AS) nastaju zbog poremećaja genomskog upisa 15q11.2-q13 domene. Ako su zbog poremećaja genomskog upisa očevi geni utišani, onda nastaje PWS, a ako su utišani geni majčinoga podrijetla nastaje AS. Glavne karakteristike PWS-a su novorođenačka hipotonija, pretilost i prekomjerno jedenje, zaostajanje u rastu i razvoju, i hipogonadotropni hipogonadizam. Karakteristike AS-a su zastoj u razvoju, teško oštećenje govora, poremećaj ravnoteže i tipično ponašanje u smislu pretjeranoga smijanja i napadaja smijeha. Poremećaji genomskog upisa na kromosomu 11p15 uzrokuju Beckwith-Wiedemann sindrom (BWS) i Silver-Russell sindrom (SRS). Ako se inaktiviraju majčini geni, nastaje BWS, a SRS nastaje ako se inaktiviraju očevi geni. Temple sindrom (TS) i Kagami-Ogata sindrom (KOS) nastaju zbog poremećaja genomskog upisa 14q32 domene. TS nastaje zbog inaktivacije očevih gena, a KOS zbog inaktivacije majčinih gena. BWS i KOS su povezani s prekomjernim rastom organizma i omfalokelom, a BWS je još udružen i s povećanim rizikom za nastanak embrionalnih tumora. SRS i TS povezani su s niskom porođajnom masom, niskim rastom, trokutastim oblikom lica i klinodaktilijom, ali postoje međusobne razlike. Cilj rada je opisati mehanizme nastanka UPD-ova, važnost genomskog upisa te dati pregled važnijih sindroma UPD-ova., Uniparental disomy (UPD) is a condition in which a homologous pair of chromosomes is wholly or partially derived from one parent. Further, UPD is divided into isodisomy and heterodisomy. UPD can be the cause of autosomal recessive (AR) diseases even if only one parent is a carrier, and if UPD of chromosomes 6, 7, 11, 14, 15 or 20 is present, certain syndromes can arise that are the result of gene imprinting disorders. Gene imprinting is an epigenetic mechanism that allows the expression of certain genes depending on parental origin. A disorder of gene imprinting creates an imbalance between the genes that are imprinted, which is the result of excessive activation or excessive inactivation of certain genes. In this way, UPD syndromes arise. Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by disruption of the gene imprinting of the 15q11.2-q13 domain. If the paternal genes are silenced, then PWS occurs, and if genes of maternal origin are silenced, AS occurs. The main characteristics of PWS are neonatal hypotonia, obesity and overeating, short stature and hypogonadotropic hypogonadism. AS is characterized by developmental delay, severe speech impairment, balance disorder and typical behavior in terms of excessive laughing and laughing fits. Gene imprinting disorders on chromosome 11p15 cause Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS). If maternal genes are inactivated, BWS occurs, and SRS occurs if paternal genes are inactivated. Temple syndrome (TS) and Kagami-Ogata syndrome (KOS) are caused by disruption of the gene imprinting of the 14q32 domain. TS is caused by the inactivation of the paternal genes, and KOS is caused by the inactivation of the maternal genes. BWS and KOS are associated with overgrowth and omphalocele, further, BWS is also associated with an increased risk of embryonal tumors. SRS and TS are associated with low birth weight, short stature, triangular face shape and clinodactyly, but there are differences between them. The aim is to describe mechanisms of UPD formation, the importance of gene imprinting and give an overview of the most relevant UPD syndromes.

Svrha ovog diplomskog rada je prikazat rijetku genetičku bolest Bosch-Boonstra-Schaaf sindrom optičke atrofije. Bosch-Boonstra-Schaaf sindrom optičke atrofije je monogenski autosomno dominantni poremećaj NR2F1 gena, karakteriziran zaostajanjem u razvoju, intelektualnim zaostajanjem i optičkom atrofijom. NR2F1 gen se nalazi na dugom kraku 5. kromosoma, na poziciji 5q15. Protein kojeg NR2F1 gen kodira vrši funkciju nuklearnog hormonskog receptora te regulatora transkripcije. Patogene varijante gena i delecije koje zahvaćaju kromosom 5 dovode do pojave kliničke slike Bosch-Boonstra-Schaaf sindroma. Od oftalmoloških kliničkih značajki opisane su abnormalnosti optičkog živca, blijedoća diska i ekskavacija diska, strabizam i latentni nistagmus, a od ostalih značajki opisane su zaostajanje u razvoju i učenju govora, hipotonija, opsesivno kompluzivni poremećaj, oromotorna disfunkcija, repetativni pokreti, značajke iz spektra autizma i poremećaja ponašanja te stanjivanje corpusa callosuma. Najtežu kliničku sliku uzrokuju patogene varijante u DNA vezujućoj domeni proteina, zatim patogene varijante koje uzrokuju prijevremeni stop kodon te frameshift, a nešto blaže kliničke slike uzrokuju potpune delecije gena i patogene varijante u ligand vezujućoj domeni proteina. U većini opisanih slučajeva bolest je nastala de novo, međutim opisana su i dva slučaja gonadnog mozaicizma. Glavni simptomi i znakovi bolesti su hipoplazija optičkog živca ili optička atrofija u kombinaciji sa zaostajanjem u razvoju ili intelektualnom zaostajanju, a konačna dijagnoza postavlja se genetičkim testiranjima. Zbrinjavanje pacijenata usmjereno je na simptome, odnosno na poboljšanje kvalitete života., The purpose of this master's thesis is to present a rare genetic disorder called Bosch-Boonstra-Schaaf optic atrophy syndrome. Bosch-Boonstra-Schaaf optic atrophy syndrome is a monogenic autosomal dominant disorder of the NR2F1 gene, characterized by developmental delay, intellectual disability, and optic atrophy. The NR2F1 gene is located on the long arm of chromosome 5, at position 5q15. The protein encoded by the NR2F1 gene functions as a nuclear hormone receptor and transcription regulator. Pathogenic gene variants and deletions affecting chromosome 5 lead to the manifestation of the clinical features of Bosch-Boonstra-Schaaf syndrome. Ophthalmological clinical features include abnormalities of the optic nerve, optic disc pallor and excavation, strabismus and latent nystagmus. Other features include developmental and speech delay, hypotonia, obsessive-compulsive disorder, oromotor dysfunction, repetitive movements, features from the autism spectrum and behavioral disorders, as well as thinning of the corpus callosum. The most severe clinical presentation is caused by pathogenic variants in the DNA-binding domain of the protein, followed by pathogenic variants that result in premature stop codons and frameshift mutations, while complete gene deletions and pathogenic variants in the ligand-binding domain of the protein lead to milder clinical phenotypes. In most described cases, the disease arises de novo, although two cases of gonadal mosaicism have been reported. The main symptoms and signs of the disease are hypoplasia of the optic nerve or optic atrophy combined with developmental delay or intellectual disability, and the final diagnosis is established through genetic testing. Patient management is focused on addressing the symptoms and improving the quality of life.

Svrha ovog rada jest prikazati najčešće aneuploidije spolnih kromosoma i ukazati na njihovu dijagnostiku, etiologiju, epidemiologiju i patofiziologiju, najčešću kliničku prezentaciju i organizaciju cjeloživotne skrbi. Aneuploidije spolnih kromosoma su numerička kromosomska aberacija koja rezultira gubitkom jednog ili dobitkom jednog ili više spolnih kromosoma. Najčešće aneuploidije spolnih kromosoma su Klinefelter sindrom (47,XXY), Turner sindrom (45,X), Triplo X sindrom (47,XXX) i XYY sindrom (47,XYY). Inaktivacija X kromosoma dešava se kako bi se izjednačila doza gena između gena spolnih kromosoma i ostatka genoma. Međutim, određeni geni izbjegavaju inaktivaciju te njihovo prekomjerno izražavanje rezultira fenotipskim abnormalnostima Klinefelter i Triplo X sindroma, dok je izražavanje tih gena slabije u Turner sindromu zbog haploinsuficijencije. Klinefelter sindrom ima veliku varijabilnost kliničke prezentacije, ali iznadprosječna visina je najčešća fenotipska prezentacija. Često imaju male testise i ginekomastiju. Postoji sklonost poteškoćama pri učenju a mnogi pokazuju nižu verbalnu inteligenciju. Djevojčice s Turner su nižeg rasta. Česte srčane anomalije su koarktacija aorte i bikuspidalni aortalni zalistak. Disgeneza gonada je česta pojava, onemogućujući početak puberteta. Kvocijent inteligencije je u rasponu normale, a postoje deficiti u vizualno-prostornim sposobnostima. Triplo X sindrom rijetko uzrokuje očite fizičke abnormalnosti. Djevojke s trostrukim X sindromom mogu imati nešto nižu inteligenciju i poteškoće u verbalnim vještinama. Dječaci sa sindromom XYY obično su viši od prosjeka te pokazuju IQ za 10 bodova niže od prosjeka. Liječenje je uglavnom simptomatsko, s posebnom pažnjom posvećenom komorbiditetima pacijenta i ranom otkrivanju bolesti. Supstitucijska terapija testosteronom koristi se kod Klinefelter sindroma, a estrogenom i hormonom rasta kod Turner sindroma., The purpose of this work is to present the most common sex chromosome aneuploidies and to discuss their diagnosis, etiology, epidemiology, and pathophysiology, as well as the most frequent clinical presentation and lifelong care organization. Aneuploidies of sex chromosomes are numerical chromosomal aberrations that result in the loss or gain of one or more sex chromosomes. The most common aneuploidies of sex chromosomes are Klinefelter syndrome (47,XXY), Turner syndrome (45,X), Triple X syndrome (47,XXX), and XYY syndrome (47,XYY). X chromosome inactivation occurs to equalize gene dosage between sex chromosome genes and the rest of the genome. However, certain genes escape inactivation, and their overexpression results in phenotypic abnormalities in Klinefelter and Triple X syndromes, while expression of these genes is lower in Turner syndrome due to haploinsufficiency. Klinefelter syndrome exhibits a wide range of clinical presentations, but above-average height is the most common phenotype. They often have small testes and gynecomastia. There is a tendency for learning difficulties, and many show lower verbal intelligence. Turner girls have short stature. Common cardiac abnormalities include coarctation of the aorta and bicuspid aortic valve. Gonadal dysgenesis is common, preventing the onset of puberty. IQ ranges within the normal range, with deficits in visual-spatial abilities. Triple X syndrome rarely causes obvious physical abnormalities. Girls with Triple X syndrome may have slightly lower intelligence and difficulties in verbal skills. Boys with XYY syndrome are usually taller than average and exhibit an IQ 10 points lower than the average. Treatment is mainly symptomatic, with special attention given to the patient's comorbidities and early disease detection. Testosterone replacement therapy is used in Klinefelter syndrome, while estrogen and growth hormone therapy are used in Turner syndrome.

Cilj rada je opisati mehanizam djelovanja i kliničku primjenu genske terapije. Genska terapija je biološki medicinski proizvod s aktivnom supstancom koja se sastoji od rekombinantne nukleinske kiseline i primjenjuje se u ljudima s ciljem regulacije, popravka, nadomještanja, dodavanja ili brisanja genske sekvence. Prijenos egzogenog genetičkog materijala u stanice ili transfekcija se može odvijati in ex vivo ili in vivo. Ex vivo pristup uključuje izdvajanje stanica ili tkiva iz pacijenta, genetičku modifikaciju i kultivaciju izdvojenih stanica ili tkiva izvan tijela i zatim vraćanje istih u tijelo pacijenta. In vivo pristup podrazumijeva primjenu genskog terapeutika direkno u tijelo pacijenta, njegovu distribuciju u tkiva, transfekciju ciljnih stanica i genetičku modifikaciju tih stanica. Metode transfekcije mogu biti fizikalne, kemijske i biološke. Većina genske terapije koja se danas primjenjuje u kliničkoj praksi za transfekciju stanica koristi kemijske (nebiološke) i biološke vektore u obliku lipidnih nanočestica i virusa. Vektori su prijenosnici genetičkog materijala koji štite i dopremaju nukleinske kiseline do ciljnih stanica. Cilj genske terapije može biti dodavanje gena, utišavanje gena, uređivanje gena ili eliminacija tumorskih stanica. Dodavanje gena je metoda genske terapije namijenjena liječenju bolesti kod kojih nedostaje izražavanje produkta gena ili se stvara nefunkcionalni produkt. Utišavanjem gena nastoji se ukloniti ili smanjiti ekspresija nekog gena jer njegov produkt prekomjerno izražen i/ili toksičan. Uređivanje gena omogućuje izmjenu DNK sekvence gena, čime se utjecati na ekspresiju proteina, ali i strukturu proteinskog produkta na genomskoj razini. Metoda eliminacije tumorskih stanica temelji se na primjeni onkotropnih virusa koji induciraju staničnu smrt ili pojačavaju imunosnu reakciju domaćina na tumor., The goal of this review is to describe the mechanism of action and clinical applications of gene therapy. Gene therapy is a biological medical product which contains an active substance consisting of recombinant nucleic acid that is used in humans with the goal of regulating, repairing, replacing, adding or deleting the gene sequence. The transfer of exogenous genetic material into cells or transfection can take place ex vivo or in vivo. The ex vivo approach involves extracting cells or tissue from the patient, genetically modifying and cultivating the extracted cells or tissue outside the body and then returning them to the patient's body. The in vivo approach involves the application of gene therapeutics directly into the patient's body, distribution to tissues, transfection of target cells and genetic modification of these cells. Transfection methods can be physical, chemical and biological. Most gene therapy products used in clinical practice today use chemical (non-biological) and biological vectors in the form of lipid nanoparticles and viruses for transfection. Vectors are carriers of genetic material that protect and deliver nucleic acids to target cells. The aim of gene therapy can be to add genes, silence genes, edit genes or eliminate tumor cells. Gene addition is a method of gene therapy intended for the treatment of diseases in which the expression of the gene product is lacking or a non-functional product is created. The goal of gene silencing is to remove or reduce the expression of a gene because its product is overexpressed and/or toxic. Gene editing makes it possible to change the DNA sequence of a gene, thereby influencing protein expression, as well as the structure of the protein product at the genomic level. The method of eliminating tumor cells is based on the application of oncotropic viruses that induce cell death or enhance the host's immune response to the tumor.

Epigenetic changes include all modifications affecting expression of genes without changing the nucleotide sequence of the genome. Most studied epigenetic changes include DNA methylation, histone alterations and non-coding RNAs (ncRNA). DNA methylation is an important epigenetic mark, protecting the genome during gametogenesis and early embryo development. Demethylation process is a genome-wide event, taking place in two distinct waves during gametogenesis. The first event helps restore naïve pluripotency of the zygote, while the second event aids the loss of parental epigenetic memory and facilitates specification of gametes. Histone modifications were recognized in murine and human primordial germ cells where their subsets condense chromatin protecting it from dynamic changes taking place during gamete maturation. Deacetylation of histones was recognized as an important prerequisite of chromosomal segregation during metaphase II. Germline-specific ncRNAs, piRNA is important in inhibiting transposon activity during gametogenesis, protecting overall genome stability. All epigenetic changes are prone to disruption, especially by exogenous factors. In recent years, connection between ARTs and its effects on epigenome remodeling of gametes gained importance. The idea was that medical procedures done to oocytes with the aim of achieved pregnancy could harm these delicate processes and lead to disease. Even though this hypothesis requires more research, a subtle link between the two was discovered. The aim of this thesis is to mention the major epigenetic modifications crucial for normal oocyte and embryo development, all while highlighting their role in reproductive disorders and ART.

Genetics is rapidly advancing, with new technologies revolutionizing research. However, opportunities provided by NGS seemingly cannot be replicated in clinics, due to lack of genetic expertise among specialists. NGS is a DNA sequencing method, allowing rapid detection of genetic variants in probands by comparison to a reference genome. NGS is an important diagnostic tool in the field of Neurology, as the prevalence of genetic factors in etiology is high, such as in a multitude of causes for movement disorders, developmental delay and morphological brain anomalies, epilepsy, and other neurological diseases. The aim of this study was to assess the usefulness of NGS. A retrospective study was per-formed, evaluating the indications for NGS in Neurology and pediatric Neurology from 2018-2022, at the University of Rijeka. Of 116 NGS tests performed across 5 years, 31 pathological variants could be detected across 27 genes, providing a diagnosis for 27 patients (23%). The highest outcome of posi-tive genetic results occurred in developmental anomalies, while the lowest, compared to negative findings, was in dystonia. Genetic movement disorders were found to be more frequent in the younger population, which is in concordance with previous research. Diagnosed developmental delay is a strong indicator for NGS, especially with concomitant structural brain malformations, sei-zures, or movement disorders. NGS is the gold standard for the diagnosis of primary epi-lepsy, indicating that in Rijeka epilepsy is an underrepresented indication for NGS. In conclusion, the guidelines for applications of NGS in Neurology could be optimized, with emphasis on genetic education of neurologists.

Modern teaching and learning in biomedical education require introducing new learning methods with students in focus. Student-oriented pedagogies represent new approaches in the European higher education area, in particular for biomedical studies. Their introduction strives to modernize biomedical education and increase its quality. Personalized, predictive, participatory, and preventive (P4) medicine is revolutionizing medical care in all its aspects. However, the appropriate training that develops the P4 medicine understanding and the skills to implement this new approach needs to be improved in biomedical studies. Various initiatives are promoting new innovative pedagogies in biomedical education, striving to develop research, knowledge, and transversal skills, crucial for the students of the 21st century. Erasmus+ project “Personalized Medicine Inquiry-Based Education - PROMISE” in partnership with five European countries Mediterranean Institute for Life Sciences (Croatia), University of Split (Croatia), University of Zagreb (Croatia), University Pompeu Fabra (Spain), European Alliance for Personalized Medicine (Belgium) and Tamara Milosevic (France) tried to achieve “P4 Education” in biomedical studies. The target group of the project was students from Croatia and Spain. The main objective of the PROMISE project was to prepare students in different biomedical fields, such as biology, biotechnology, pharmacy, and medicine, for the rapidly changing landscape of medical practice and research by creating innovative inquiry-based teaching tools in an online format on the principles of P4 Medicine and Responsible Research and Innovation (RRI). During the project, the partnership developed and implemented the PROMISE program with four online modules, each dealing with one element of P4 Medicine, supplemented with in-person learning expeditions held in Paris, Split, and Zagreb where students deepened their knowledge and skills crucial for their future careers in the biomedical field. Students, after finishing the course, identified several key elements as high-quality content: 1) relevant topics for their future career, 2) raised awareness about the importance of P4 Medicine, 3) relevance of integration with different disciplines, and 4) opportunity to develop transversal skills. Students evaluated the PROMISE program as excellent regarding the methodology used, acquired knowledge, and skills. As a result of their satisfaction with the project activities, students created their youth association through which they are now raising awareness and educating others about P4 Medicine and RRI principles. The project results were evaluated by external evaluators and achieved a high score of 94/100 for project implementation.

Napretkom genetičke tehnologije, genomike i bioinformatike znanje medicinske genetike postaje sve nužnije i korisnije u svakodnevnoj praksi studenata, liječnika, drugih stručnjaka i zdravstvenih djelatnika. Za dobro funkcioniranje multidisciplinarnog tima koji uključuje medicinske genetičare i druge stručnjake važno je poznavanje vokabulara medicinske genetike te alata za dijagnostiku. Upravo su glavni alati za dijagnostiku genetičkih poremećaja dijagnostičke i edukativne baze podataka genetičkih bolesti. Većina takvih baza slobodno je dostupna na internetu, a pružaju relevante informacije temeljene na dokazima. Genetičke baze podataka imaju dvije osnovne funkcije, edukativnu i dijagnostičku. Svrha ovog rada je dati pregled edukativnih i dijagnostičkih elektroničkih baza podataka s ciljem omogućavanja njihovog lakšeg korištenja te uputiti čitatelja gdje i na koji način potražiti informacije o genetičkim poremećajima. Poznavanje genetičkih baza podataka, njihovo razumijevanje i korištenje ima nevjerojatnu vrijednost za današnju i buduću medicinsku praksu. U prvom dijelu rada prikazan je pregled i upute za korištenje najznačajnijih edukativnih elektroničkih genetičkih baza podataka, uključujući OMIM, GeneReviews, Orphanet te PharmGKB. U drugom dijelu rada slijedi kratkih pregled najčešće korištenih dijagnostičkih elektroničkih genetičkih baza podataka, uključujući Human Phenotype Ontology, Face2Gene, ClinVar, gnomAD te Decipher., With the advancement of genetic technology, genomics and bioinformatics, knowledge of medical genetics is becoming more and more necessary and useful in the daily practice of students, doctors, health professionals and others. Knowledge of medical genetics vocabulary and diagnostic tools is important for the proper functioning of a multidisciplinary team that includes medical geneticists and other experts. Diagnostic and educational databases of genetic diseases are the main tools for diagnosing genetic disorders. Most such databases are freely available online and provide relevant evidence-based information. Genetic databases have two basic functions, educational and diagnostic. The purpose of this paper is to provide an overview of educational and diagnostic electronic databases to facilitate their use and instruct the reader where and how to look for information about genetic disorders. Knowledge of genetic databases, their understanding and use is of incredible value for current and future medical practice. The first part of this paper presents an overview and instructions for using the most important educational electronic genetic databases, including OMIM, GeneReviews, Orphanet and PharmGKB. The second part of the paper follows a brief overview of the most used diagnostic electronic genetic databases, including Human Phenotype Ontology, Face2Gene, ClinVar, gnomAD, and DECIPHER.

Maligna hipertermija (MH) farmakogenetička je bolest koja se nasljeđuje autosomno dominantno i ima nepotpunu penetrabilnost. Njezina je procijenjena učestalost 1:100 000 – 1:250 000 u općoj populaciji. Varijante sekvence gena koji su uključeni u regulaciju otpuštanja kalcija iz sarkoplazmatskog retikuluma uzrokuju nastanak ove bolesti. Trenutno je priznato 48 varijanti sekvence gena za rijanodinski RyR1 receptor koji se nalazi na 19. kromosomu i 2 za dihidropiridinski receptor (CACNA1S - engl. Calcium Voltage-Gated Channel Subunit Alpha1 S), a od spominju se još i varijante sekvence STAC3 (engl. SH3 And Cysteine Rich Domain) gena. Zbog tih varijanti sekvence dolazi do promijenjenog odgovora na hlapljive anestetike i sukcinilkolin, koji izazivaju pojačano otpuštanje kalcijevih iona iz sarkoplazmatskog retikuluma i posljedično mišićne kontrakcije koje pak dovode do hipermetaboličkog stanja. U praksi se to očituje povišenjem tjelesne temperature, spazmom mišića, razvojem acidoze, hipoksijom, hiperkapnijom, acidozom i tahikardijom. Komplikacije koje se mogu javiti jesu diseminirana intravaskularna koagulopatija, akutno bubrežno zatajenje i multiorgansko zatajenje. Klinička se dijagnoza postavlja na temelju Kriterija za kliničko stupnjevanje maligne hipertermije koji su bazirani na kliničkoj slici, dok se sama dijagnoza postojanja MH zasniva na testu kontrakture i farmakogenetičkom testiranju. Kliničko se zbrinjavanje sastoji od 4 glavne komponente – uklanjanja okidajućeg agensa, primjene dantrolena, snižavanja tjelesne temperature i zbrinjavanja komplikacija. Cilj ovog diplomskog rada je prikazati farmakogenetičku bolest – malignu hipertermiju, ukazati na njezinu genetičku pozadinu, opisati kliničku sliku i dijagnostički postupak., Malignant hyperthermia is an autosomal dominant pharmacogenetic disease with incomplete penetrance. Its prevalence is estimated to be 1:100 000 – 1:250 000 in the general population. Variants of genes involved in sarcoplasmic calcium release cause this disorder. Currently, there are 48 variants of the RyR1 gene located on the 19th chromosome, and 2 variants of CACNA1S (Calcium Voltage-Gated Channel Subunit Alpha1 S) gene that are accepted as disease-causative genes but variants of the STAC3 (SH3 And Cysteine Rich Domain) gene are also mentioned in literature. Because of these variants, there is an altered response to volatile anaesthetics and succinylcholine leading to an increased release of calcium ions from the sarcoplasmic reticulum thus causing a hypermetabolic state. Clinically, this state manifests as increase in core body temperature, muscle spasm, hypoxia, hypercapnia, acidosis, and tachycardia. The complications that can occur include disseminated intravascular coagulopathy, acute kidney failure and multiorgan failure. The clinical diagnosis is established following the Criteria for clinical grading of malignant hyperthermia proposed by Larach et al. (1994) and Rosenberg et al. (2015). These criteria are based upon the clinical presentation. For the final diagnosis, contracture test and/or pharmacogenetic testing are needed. Treatment follows four base principles – discontinuation of triggering agent, admission of dantrolene, lowering of core body temperature and treating complications. The aim of this graduate thesis is to present a pharmacogenetic disease – malignant hyperthermia, to indicate its genetic background, describe the clinical presentation and diagnostic procedure.

Delecije i duplikacije najčešće su strukturne varijacije genoma čovjeka te se zajedno nazivaju varijacije broja kopija (engl. copy number variation, CNV). CNV se definira kao dodatak ili gubitak dijela DNK u usporedbi s referentnim humanim genomom. Veličina im varira od 1.000 parova baza do nekoliko milijuna parova baza. Rekurentni mikrodelecijski sindromi nastaju promjenama u količini ukupne DNK-a uvijek na istom mjestu u genomu te dovode do prepoznatljivih fenotipova s dobro definiranom korelacijom genotip-fenotip. Nastaju malim delecijama koje iznose manje od 5 Mb dijelova kromosoma te se ne mogu detektirati kariotipizacijom. Ovisno o vrsti rekurentnog mikrodelecijskog sindroma, pacijenti najčešće imaju intelektualno zaostajanje i moguća obilježja poremećaja autističnog spektra, izrazite značajke ponašanja, poremećaje spavanja te kraniofacijalne i skeletne dismorfije. Genomski poremećaji se istražuju i otkrivaju metodom komparativne genomske hibridizacije na mikročipu te se dodatno mogu potvrditi neovisnom metodom kao što je FISH, MLPA ili kvantitativni PCR., Deletions and duplications are the most common structural variations of the human genome and referred to as copy number variations (CNV). CNV is defined as the addition or loss of DNA amount compared to the reference human genome. Their size varies from 1.000 base pairs to several million base pairs. Recurrent microdeletion syndromes are caused by changes in the amount of total DNA always at the same place in the genome and lead to recognizable phenotypes with a well-defined genotype-phenotype correlation. They are formed by small deletions that are less than 5 Mb of chromosome parts and can not be detected by karyotyping. Depending on the type of recurrent microdeletion syndrome, patients most often have intellectual retardation and possible features of autism spectrum disorders, mood or sleep disorders and craniofacial or skeletal dysmorphia. Genomic disorders are investigated and detected by the method of comparative genomic hybridization on a microchip and can be further confirmed by an independent method such as FISH, MLPA or quantitative PCR.

Znanstveni napredak u području genetike otvorio je nove mogućnosti u dijagnostici nasljednih kardiovaskularnih bolesti, kao što je genetičko testiranje. Prema indikaciji, kod kardiovaskularnih bolesti sa genetičkim uzrokom, najčešće se primjenjuju dijagnostičko i prediktivno testiranje. Najčešće kardiovaskularne bolesti, kod kojih se primjenjuje genetičko testiranje uključuju: kardiomiopatije, kanalopatije, aortopatije i obiteljsku hiperkolesterolemiju. Genetičko testiranje kod navedenih bolesti najčešće se provodi kod osoba sa sumnjom na dijagnozu ili kod već postavljene kliničke dijagnoze kako bi se potvrdila. Također se preporuča i testiranje u članova obitelji i rođaka, najprije onih koji pokazuju simptome ili znakove bolesti, ali i u asimptomatskih osoba. Osobe sa pozitivnim rezultatom na genetski poremećaj, treba redovito klinički pratiti. Prije genetičkog testiranja, kao i nakon njega, važno je provesti genetičko savjetovanje u osoba koje se testiraju. Genetičko testiranje na kardiovaskularne bolesti dostupno je u brojnim zdravstvenim ustanovama diljem svijeta, najviše u SAD-u i Zapadnoj Europi. U Hrvatskoj je ono dostupno u nekoliko privatnih zdravstvenih ustanova isključivo u obliku genetičkog testiranja neposredno ponuđenog potrošaču (DTC)., Scientific advances in genetics have opened up new possibilities in the diagnosis of hereditary cardiovascular diseases, such as genetic testing. According to the indication, in cardiovascular diseases with a genetic cause, diagnostic and predictive testing is most often used. The most common cardiovascular diseases in which genetic testing is used include; cardiomyopathies, channelopathies, arthropathies, and familial hypercholesterolemia. Genetic testing for these diseases is most often performed on people with a suspected diagnosis or an already established clinical diagnosis in order to confirm it. It is also recommended to test family members and relatives, first of all, those who show symptoms or signs of the disease, but also in asymptomatic people. People with a positive result for a genetic disorder should be monitored regularly in the clinic. Before and after genetic testing, it is important to conduct genetic counseling for the people being tested. Genetic testing for cardiovascular disease is available in a number of healthcare facilities around the world, most notably in the United States and Western Europe. In Croatia, it is available in several private health care institutions in the form of direct-to-consumer tests.

Cilj ovog istraživanja bio je provesti sveobuhvatnu analizu broja NGS testova te utvrditi indikacije i rezultate testiranja provedenih na Medicinskom fakultetu u Rijeci od uvođenja te dijagnostičke metode. Materijali i metode: Ovom retrospektivnom studijom obuhvaćeno je vremensko razdoblje od 2017. do 2021. godine, a uključuje analizu uputnih dijagnoza i rezultata NGS testova pacijenata, upućenih iz Kliničkog bolničkog centra Rijeka na genetičko testiranje na Medicinski fakultet u Rijeci. NGS je izveden u suradnji s Kliničkim institutom za medicinsku genetiku u Ljubljani (Slovenija), koristeći Illumina NovaSeq 6000 (Illumina Inc.). Rezultati: Tijekom 2017. godine radilo se na uspostavi sustava te su se, u tu svrhu, organizirale brojne edukacije i razgovori s kliničarima. Od travnja 2018. do prosinca 2021. godine je provedeno ukupno 118 dijagnostičkih NGS-a, od čega 8 u 2018. (7 %), 29 u 2019. (25 %), 42 u 2020. (35 %) i 39 u 2021. godini (33 %). Od 2018. godine broj pretraga raste za 425 % u 2019. godini, od 2019. do 2020. za 141 %, te od 2020. do 2021. pada za 8 %. Najčešće indikacije za testiranje bile su neuromišićne bolesti (41 %), kardiomiopatije (19 %) i multiple prirođene anomalije (15 %). Pozitivni rezultati dobiveni su u 53/118 (45 %) slučajeva,od kojih je utvrđeno 14 (26 %) vjerojatno patogenih i 26 (49 %) patogenih varijanti sekvence te 13 (25 %) varijanti nejasnog značaja. U 65/118 (55 %) slučajeva nije pronađena genetička aberacija. Od ukupnog broja pozitivnih nalaza, potvrđeno je 75 % uputnih dijagnoza te samo 34 % od ukupnog broja nalaza. Zaključak: Dobiveni rezultati ukazuju na porast broja provedenih dijagnostičkih NGS testiranja u razdoblju od 2017. do 2021. godine, što odražava povećanu svijest kliničara o potrebi genetičkog testiranja u kliničkoj praksi. Nažalost, veliki broj pogrešnih indikacija za genetičko testiranje upućuje na nužnost genetičke edukacije kliničara, u svrhu boljeg dijagnostičkog učinka., Aim: The aim of this study was to determine the number, indications and results of diagnostic NGS tests performed at the Faculty of medicine in Rijeka, Croatia since its implementation. Materials and Methods: A retrospective study was performed from 2017 to 2021 and included the analysis of referral diagnoses and NGS test reports of patients who were referred to the Faculty of Medicine in Rijeka for diagnostic NGS testing from Clinical Hospital Center Rijeka. NGS was performed in collaboration with the Clinical Institute of Genomic Medicine in Ljubljana (Slovenia), using Illumina NovaSeq 6000 (Illumina Inc). Results: During 2017 was worked on the establishment of the system, and for this purpose, numerous educations and interviews with clinicians were organized. From April 2018 to December 2021, a total od 118 diagnostic NGS were performed, including 8 in 2018 (7 %), 29 in 2019 (25 %), 42 in 2020 (35 %) and 39 in 2021 (33 %). From 2018, the number of NGS testing increase by 425% in 2019, from 2019 to 2020 by 141%, from 2020 to 2021 it decrease by 8%. The most common indications for testing were neuromuscular diseases (41 %), cardiomyopathies (19 %) and multiple congenital anomalies (15 %). Positive test results were obtained in 53/118 (45 %) cases in whom likely pathogenic (26 %) or pathogenic sequence variants (49 %) were determined. Class 3 sequence variants were identified in 13 (11 %) cases. In 65/118 (55 %) cases no genetic aberration could be found. Out of the total number of positive findings, 75 % of referral diagnoses were confirmed and only 34% of the total number of findings. Conclusion: Our results show an increase in the number of diagnostic NGS tests from 2017 to 2021, which reflects the increased awarness of clinicians for the need of genomic testing in clinical practise. Unfortunately, the large number of incorrect indications for genetic testing, indicates that genetic education of clinicians is needed for an improved diagnostic yield.

Cilj: Cilj istraživanja je bio utvrditi internetsku ponudu DTC genetičkih testova u Republici Hrvatskoj s osvrtom na indikacije, prisutnost genetičkog savjetovanja i oglašavanje. Materijali i metode: Za pretraživanje internetske ponude korištena je Google tražilica u razdoblju od 3.2.2022. do 5.2.2022. godine. Ključne riječi korištene u pretraživanju bile su zasebno u svakom pretraživanju: genetičko testiranje, genetsko testiranje, gensko testiranje, genetički testovi, genetski testovi, genski testovi, genetička analiza, genetska analiza, genska analiza, prenatalna dijagnostika, prenatalni testovi, farmakogenetika, farmakogenomika, DNA testiranje, DNA testovi. Rezultati za svaku ključnu riječ pretraživani su do 15. Google stranice. Uključni kriteriji za analizu internetske stranice s DTC ponudom bili su: poliklinike, tvrtke, obrti, specijalne bolnice, laboratoriji, osiguravajuće kuće, istraživački instituti i ustanove za zdravstvenu njegu koje nude genetičke testove. Podaci koji su preuzeti i analizirani za svaku stranicu bili su: vrsta, ime i adresa internetske stranice ponuđača DTC genetičkih testova, vrste genetičkih testova prema indikaciji, uključenost genetičkog savjetovanja u DTC ponudu te način oglašavanja. Rezultati: U Republici Hrvatskoj 68 ponuđača nudi DTC testiranje. Od toga: dijagnostičko (7 ponuđača), prediktivno (1 ponuđač), određivanje statusa nositelja (0 ponuđača), farmakogenomsko testiranje (4 ponuđača), testovi probira (41 ponuđač) i testovi bez indikacije (38 ponuđača). Od toga njih 10 % nudi uslugu genetičkog savjetovanja. Oglašavanje testova je usmjereno na pozitivne učinke genetičkog testiranja. Zaključak: S obzirom na veliki broj ponuđača testova, a mnogi od njih nude testove bez nužnosti postojanja indikacije, potrebna je bolja kontrola DTC tržišta u Republici Hrvatskoj., Objective: The aim of the study was to determine the online offer of DTC genetic tests in the Republic of Croatia with reference to indications, the presence of genetic counseling and advertising. Materials and methods: Google search engine was used to search the Internet offer in the period from 3.2.2022. to 5.2.2022. years. The keywords used in the search were separate in each search: genetic testing, genetic testing, genetic testing, genetic testing, genetic testing, genetic testing, genetic analysis, genetic analysis, genetic analysis, prenatal diagnosis, prenatal testing, pharmacogenetics, pharmacogenomics, DNA testing, DNA tests. The results for each keyword were searched up to the 15th Google page. Including criteria for analyzing the DTC website were: clinics, companies, crafts, special hospitals, laboratories, insurance companies, research institutes, and health care facilities that offer genetic testing. The data downloaded and analyzed for each page were: type, name and address of the DTC genetic testing provider's website, types of genetic testing as indicated, inclusion of genetic counseling in the DTC offer, and method of advertising. Results: In the Republic of Croatia, 68 bidders offer DTC testing. Of which: diagnostic (7 bidders), predictive (1 bidder), carrier status determination (0 bidders), pharmacogenomic testing (4 bidders), screening tests (41 bidders) and non-indication tests (38 bidders). Of these, 10% offer a genetic counseling service. Advertising is focused on the positive effects of genetic testing. Conclusion: Given the large number of test providers, and many of them offer tests without the need for an indication, better control of the DTC market in the Republic of Croatia is needed.