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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

"Slagalica nasljeđa" - priručnik za opismenjavanje iz medicinske genetike ima tri namjene. Prije svega, on je edukativna slikovnica za studente, liječnike i pacijente, ali i druge zainteresirane pojedince jer su u njoj kroz ilustracije objašnjene osnove genetike čovjeka, kao i osnove medicinske genetike. Od toga kako prepoznati osobu s genetičkim poremećajem, kako nastaju i koje vrste genetičkih poremećaja postoje pa sve do toga na koji ih način možemo dijagnosticirati. Nadalje, nakon svake ilustracije na pojedinoj stranici nalaze se definicije 79 pojmova iz medicinske genetike koje čine tezaurus za studente, liječnike i pacijente koji se na bilo koji način susreću s genetičkim poremećajima. Naposljetku, ova knjiga sadrži i primjere rečenica u koje su ubačeni stručni pojmovi iz medicinske genetike, a koji su namijenjeni studentima prilikom savladavanja komunikacijskih vještina na kolegiju Medicinska genetika, ali i liječnicima prilikom informiranja svojih pacijenata o (mogućem) genetičkom poremećaju. Uz kreatoricu ideje i urednicu izdanja, doc. dr. sc. Ninu Perezu, autori izdanja su studenti šeste godine Integriranog preddiplomskog i diplomskog sveučilišnog studija Medicina i prof. dr. sc. Saša Ostojić.

Supplemental Material, sj-pdf-1-brn-10.1177_10998004211043571 for Maternal LINE-1 DNA Methylation in Early Spontaneous Preterm Birth by Anita Bari��i��, Aleksandra Stankovi��, Ljiljana Stojkovi��, Nina Pereza, Sa��a Ostoji��, Ana Peterlin, Borut Peterlin and Jadranka Vranekovi�� in Biological Research For Nursing

Introduction: The deficiency of vitamin D has been associated with premature birth. The effects of vitamin D are mediated by its receptor (VDR), which is encoded by the VDR gene. Both VDR gene polymorphisms and DNA methylation play important roles during normal and pathological pregnancy. The aim of this study was to evaluate whether maternal VDR gene polymorphisms and long interspersed nucleotide elements 1 (LINE-1) DNA methylation, alone or in combination, are a risk factor for idiopathic spontaneous preterm birth (ISPTB) in Croatian and Slovenian women. Material and methods: This case-control study included 50 women who delivered spontaneously early preterm (23-336/7 weeks of gestation) and 50 control women who delivered at term. The FokI (rs2228570), ApaI (rs7975232), Bsml (rs1544410), TaqI (rs 731236), and Cdx2 (rs11568820) single nucleotide polymorphisms (SNPs) in the VDR gene were identified using the combination of polymerase chain reaction and restriction fragment length polymorphism. Quantification of LINE-1 DNA methylation was determined using the MethyLight method. Results: There was no significant difference observed in genotype and allele frequencies of VDR gene polymorphism between women with ISPTB and control women (P > 0.050). Moreover, no significant differences were found in inheritance models between groups of subjects. The values of LINE-1 DNA methylation in patients with ISPTB did not significantly differ compared to the control group (P = 0.767). Additionally, no association was observed in DNA methylation between any of the analyzed genotypes of VDR gene polymorphisms (P > 0.050). Conclusion: The results of our study indicate that VDR gene polymorphisms are not associated with the occurrence of ISPTB. In addition, based on the LINE-1 quantification, DNA methylation is not associated with ISPTB nor with VDR gene polymorphisms. Considering the number of patients enrolled, further research is needed to detect and clarify the role of DNA methylation and VDR gene polymorphisms in ISPTB.

Genetic variation in the maternal vitamin D receptor FokI gene as a risk factor for recurrent pregnancy loss

Association between vitamin D receptor sequence variants and obesity/metabolic syndrome: systematic review

Goal: Preterm birth (PTB) is defined as birth before the 37th completed week of gestation and is the leading cause of neonatal mortality and morbidity. Although up to 25% of PTBs are medically induced, the majority is initiated spontaneously (SPTB or idiopathic PTB), accounting for approximately 50 % of all cases. Tumor necrosis factor α (TNFα) is a critical proinflammatory cytokine involved in the remodeling of cervix and fetal membranes by promoting collagen degradation. The aim of our study was to evaluate the potential association of TNFα rs361525 -238 G/A and TNFα rs1800629 -308 G/A gene polymorphisms with SPTB in Slavic women, and their contribution to clinical characteristics of women with SPTB. Material and methods: A total of 138 women with SPTB and 139 women with term delivery were included in a case-control study. All women with SPTB had singleton pregnancies following natural conception and spontaneous initiation of PTB before the 37th week of gestation. None of the women had known risk factors for PTB, including diabetes, hypertension, kidney disease, autoimmune conditions, allergic diseases, birth canal infections, in vitro fertilization and complications of pregnancy. The control group consisted of 139 women who had a term birth of a singleton baby after an uncomplicated pregnancy and were of the same age and parity as patients. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism methods. Results: We found a statistically significant higher frequency of the TNFα -238 AG genotype (X2=7.32 ; P=0.025) and A allele (X2=7.48 ; P=0.006) in women with SPTB compared to controls. Additionally, the odds for SPTB in women were increased under the dominant genetic model (AA+AGvsGG: OR=3.20 ; 95% CI=1.30- 7.83 ; P=0.011). There were no statistically significant differences in genotype and allele frequencies of TNFα -308 G/A between SPTB patients and controls. Moreover, no significant associations of the TNFα -308 G/A and SPTB occurred. None of the polymorphisms contributed to the clinical characteristics of women with SPTB. Conclusion: Our results indicate that maternal TNFα rs361525 -238 G/A might be susceptibility factor for SPTB.

Aim: The aim of this study was to evaluate the potential association between spontaneous or idiopathic PTB (SPTB) and DNMT3B gene polymorphisms in Slavic women, and their contribution to clinical characteristics of women with SPTB and their new-borns (family history of PTB, maternal smoking before pregnancy, maternal age, gestational week at delivery and fetal birth weight). Patients and methods: A total of 162 women with SPTB and 162 women with term delivery were included in a case-control study. Genotyping of DNMT3B rs1569686 and DNMT3B rs2424913 single nucleotide polymorphisms was performed using polymerase chain reaction and restriction fragment length polymorphism methods. Results: DNMT3B rs1569686 and rs2424913 minor alleles (T) were significantly more frequent in women with familial PTB than non-familial PTB, and contributed to a 3.30 and 3.54 increased odds for familial PTB under dominant genetic models (95 % CI = 1.53-7.14, P = 0.003 and 95 % CI = 1.56-8.01, P = 0.002). Furthermore, the DNMT3B rs1569686 and rs2424913 T alleles were significantly more frequent in women with SPTB who smoked before pregnancy, reaching the most significant association under additive genetic models (OR = 6.86, 95 % CI = 2.25-20.86, P ˂ 0.001 and OR = 3.77, 95 % CI = 1.36-10.52, P = 0.011). Conclusion: The DNMT3B rs1569686 and rs2424913 gene polymorphisms in Slavic women might be associated with a positive family history of PTB and smoking status before pregnancy.

Aim: Recurrent pregnancy loss (RPL) is a reproductive disorder defined as the loss of two or more pregnancies from the time of conception until 24 weeks of gestation. Despite the fact that several mechanisms have been previously described for the pathogenesis of RPL, the causes of approximately 50% remain unknown. However, recent studies indicate association of vitamin D with adverse pregnancy outcome, including RPL. The vitamin D receptor (VDR) is a crucial mediator of the pleiotropic cellular effects of vitamin D. It's function is influenced by several single nucleotide polymorphisms (SNPs). The main objective of the present study was to assess whether three different maternal VDR SNPs are associated with the risk of RPL in Slovenian and Croatian women. Methods: A case – control study including 320 women was designed to examine the potential association of VDR polymorphisms (FokI rs222857, Cdx2 rs115688 and Taq1 rs731236) with RPL. Genotyping was performed using PCR-RFLP methods. Results: We found a statistically significant higher frequency of the FokI rs222857 CC genotype (X2=6.61, P=0.036) and C allele (X2=5.93, P=0.015) in women with RPL compared to controls. Additionally, the odds for RPL were increased under the recessive (CCvsCT+TT: OR=1.78 ; 95% CI=1.12-2.82 ; P=0.015) and codominant genetic models (CCvsTT: OR=2.21 ; 95% CI=1.08-4.53 ; P=0.029 ; CCvsCT: OR=1.68 ; 95% CI=1.04-2.72 ; P=0.036). Furthermore, Taq1 rs731236 C allele showed a statistically significant higher frequency in women with RPL compared to controls (X2=4.13, P=0.042). Conclusion: Our results suggest that the CC genotype of the FokI rs222857 polymorphism in women might be a genetic marker for RPL.

Aim: Preterm birth (PTB) is defined as birth of a new-born prior to the completed 37th week of gestation. Prior studies confirmed the association between low levels of vitamin D and increased risk of PTB. Considering that polymorphisms of vitamin D receptor (VDR) gene may modify the effects of vitamin D, several studies investigated the potential association between FokI and ApaI single nucleotide polymorphisms of the VDR gene and PTB in different races. The aim of our study was to evaluate the association between FokI and ApaI polymorphisms of the VDR gene and PTB in European Caucasian women, as well as their effect on clinical characteristics of women with PTB and their new-borns (smoking, family history of PTB, maternal and gestational age at delivery, new-born birth weight). Patients and methods: A case-control study was conducted in 113 women with spontaneous PTB (SPTB ; PTB with intact membranes) and 119 women with term delivery. Genotyping of FokI and ApaI polymorphisms of the VDR gene were performed using polymerase chain reaction and restriction fragment length polymorphism methods. Results: No statistically significant differences were found in the distribution of genotype or allele frequencies of tested polymorphisms between patients and controls. We found a statistically significant effect of FokI polymorphism on new-born birth weight in women with SPTB using two-way ANOVA: Factorial design with Scheffe test (F=4.53, P=0.013), with the lowest birth weight identified in mothers carrying the FokI TT genotype (P=0.021). There was no statistically significant interaction between the FokI and ApaI polymorphisms on birth weight. Neither polymorphism was associated with any other clinical characteristic of women with SPTB and their new-borns. Conclusion: We determined that the TT genotype of the VDR FokI polymorphism is associated with new-born birth weight in European Caucasian women with SPTB.

Aim: Recurrent spontaneous abortion (RSA) is defined as three or more consecutive pregnancy losses before the 22nd week of gestation. It affects approximately 1% of couples and can be caused by several factors. However, the cause remains unidentified in about 50% of the cases, which are classified as idiopathic (IRSA). Among various possible etiological factors, aberrant DNA methylation has been suggested to be one of the possible causes of IRSA. Considering the growing evidence of the important roles of DNA methylation in gametogenesis and early pregnancy, as well as the results of multiple studies that indicate abnormal methylation patterns in the endometrium, spermatozoa and placenta of patients with IRSA, our aim was to investigate the potential association of DNA methyltransferase gene polymorphisms (DNMT1 rs2228611, DNMT3A rs1550117 and DNMT3B rs1569686) with IRSA in Slovenian reproductive couples. Patients and methods: 146 couples with ≥3 idiopathic spontaneous abortions and 149 control women and men were included in this case-control study. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism methods. Results: We found a statistically significant higher frequency of the DNMT3B rs1569686 GG genotype (X2=7.37, P=0.025) and G allele (X2=6.33, P=0.012) in women with IRSA compared to controls. Additionally, the odds for IRSA in women were increased under the recessive genetic model (GGvsTG+TT: OR=1.92 ; 95% CI=1.18-3.09 ; P=0.008). There were no statistically significant differences in genotype and allele frequencies of any other tested polymorphism between IRSA patients and controls. Moreover, no significant associations occurred between the DNMT1 rs2228611 and DNMT3A rs1550117 polymorphisms and the risk of IRSA. Conclusion: Our results suggest that the GG genotype of the rs1569686 polymorphism in the DNMT3B gene in women might be a genetic marker for IRSA.

Aim: Preterm birth (PTB) is a birth that occurs before the 37th week of gestation and is the leading cause of neonatal mortality and morbidity. DNA methyltransferases (DNMTs) establish DNA methylation patterns at specific genome regions and contribute to gene regulation. Previous studies have reported on an association between spontaneous PTB (SPTB ; birth with intact membranes) and epigenetic changes (i.e. methylation levels) in maternal blood, placenta and cord blood. Additionally, certain DNMT3B gene polymorphisms in women were found to be associated with an increased risk for SPTB. The aim of this study was to evaluate the potential association between SPTB and DNMT1, 3A, 3B and 3L gene polymorphisms in European Caucasian women, and their contribution to clinical characteristics of women with SPTB and their new-borns. Patients and methods: A total of 113 women with SPTB and 119 women with term delivery were included in a case-control study. Genotyping of DNMT1 rs2228611 A/G, DNMT3A rs1550117 A/G, DNMT3B rs1569686 G/T and DNMT3L rs2070565 A/G single nucleotide polymorphisms was performed using polymerase chain reaction and restriction fragment length polymorphism methods. Results: No statistically significant differences were found in the distribution of genotype or allele frequencies of tested polymorphisms between patients and controls. However, the DNMT3B rs1569686 minor allele (T) was more frequent in women with familial SPTB than women with non-familial SPTB (Χ2=7.65, P=0.006), contributing to a 4.02 increased odds for familial SPTB under the dominant genetic model (TG+TTvsGG) (95% CI=1.56-10.40, P=0.004). None of the other polymorphisms contributed to the clinical characteristics of women with SPTB and their new-borns (family history of SPTB, maternal and gestational age at delivery, fetal birth weight). Conclusion: The DNMT3B rs1569686 T allele in European Caucasian women might be associated with a positive family history of SPTB.