Genetic aspect of hearing impairment

Razvoj slušnog aparata je veoma složen proces koga uslovljava me�����usobno delovanje genomskog programa tj. genetičkih instrukcija za anatomo-funkcionalno strukturiranje aparata čula sluha i faktora sredine, koji ga omogućavaju i usmeravaju u toku embrionalnog, fetalnog i nakon toga tokom postnatalnog razvoja. Greške ili deficijencije, i štetno faktorsko delovanje jednog i/ili drugog, iskazuje se u kompleksu oštećenja sluha. Najčešći uzročni faktori potiču iz genoma, genetičke strukture individue. Procenjeno je da više od 50% svih vrsta gubitaka sluha ima substancijalno genetičku komponentu. Oštećenje sluha, kao najčešći senzorni poremećaj, genetički je vrlo heterogen. Mapiranja i identifikacija gena sa osobenim ulogama u razvoju struktura i funkcija ovog čula, podvrgnuta DNK probama, metodama direktne ili indirektne detekcije mutacija – signiraju vezu greške i oštećenja. Više stotina gena je otkriveno u mehanizmu razvoja slušnog aparata i njegove funkcije. Jedni su odgovorni svojom aktivnošću za jasno prepoznate komponente strukture i funkcije čula, drugi – preko enkodiranih proteina sadejstvuju, od modifikacija, sinteze regulatora transkripcije drugih gena, faktora rasta i dr. Identifikovani su i neki geni koji uzrokuju dominantne i recesivne oblike sindromske i/ili nesindromske gluvoće, što je u kliničkoj genetici već u domenu moguće detekcije nosioca genetičkog opterećenja, prenatalnog nalaza i predmet genetičkog savetovališta. Skrining novoro�����enčadi na slušna oštećenja dao je nedvosmisleno veliki učinak, od rane detekcije i tretmana, uz brzi napredak genetike slušnih oštećenja – svrsishodnijim pristupom, prekoncepcijskoj i prenatalnoj dijagnostici, promenom kliničkog pristupa u obradi i lečenju tih oštećenja.Development of hearing apparatus is very complex process dependent on genome program, i.e. genetic instructions for anatomical and functional structuring of hearing sense and environmental factors, both of which enable and direct it through embriological, fetal, and postnatal period. Defects or deficiencies, and harmful consequences of one and/or both, are evident in hearing impairment. The most comon causes are genome and genetic structure of an individual. It is estimated that over 50% of all hearing losses are substantially genetical. Hearing impairment, being the most common sensorial disorder, is genetically very heterogenous. Mapping and identification of genes with specific roles in the development of structures and functions of this sense, when tested with DNA analysis, with direct or indirect mutation detection – point out the link between defect and impairment. Many hundreds of genes were discovered in the mechanism of development of hearing apparatus and its function. Some are responsible for clearly recognized components of structure and function of the sense, others – through encoded proteins act together in modifications, synthesis of regulators of other gene transcriptions, growth factors, etc. Furthermore, some genes were identified which cause dominant and recessive forms of syndrome and/or nonsyndrome deafness, which is in the domain of possible detection of carrier of genetic predisposition, prenatal positive finding and the subject of genetic counseling. Screening of newborns for hearing impairment has brought a great deal, from early detection and treatment, along with fast improvement of genetics in hearing impairment – with more appropriate approach, preconceptual and prenatal diagnostics, and changes in clinical approach in treatment of those impairments

Genetic aspect of hearing impairment

Razvoj slušnog aparata je veoma složen proces koga uslovljava me�����usobno delovanje genomskog programa tj. genetičkih instrukcija za anatomo-funkcionalno strukturiranje aparata čula sluha i faktora sredine, koji ga omogućavaju i usmeravaju u toku embrionalnog, fetalnog i nakon toga tokom postnatalnog razvoja. Greške ili deficijencije, i štetno faktorsko delovanje jednog i/ili drugog, iskazuje se u kompleksu oštećenja sluha. Najčešći uzročni faktori potiču iz genoma, genetičke strukture individue. Procenjeno je da više od 50% svih vrsta gubitaka sluha ima substancijalno genetičku komponentu. Oštećenje sluha, kao najčešći senzorni poremećaj, genetički je vrlo heterogen. Mapiranja i identifikacija gena sa osobenim ulogama u razvoju struktura i funkcija ovog čula, podvrgnuta DNK probama, metodama direktne ili indirektne detekcije mutacija – signiraju vezu greške i oštećenja. Više stotina gena je otkriveno u mehanizmu razvoja slušnog aparata i njegove funkcije. Jedni su odgovorni svojom aktivnošću za jasno prepoznate komponente strukture i funkcije čula, drugi – preko enkodiranih proteina sadejstvuju, od modifikacija, sinteze regulatora transkripcije drugih gena, faktora rasta i dr. Identifikovani su i neki geni koji uzrokuju dominantne i recesivne oblike sindromske i/ili nesindromske gluvoće, što je u kliničkoj genetici već u domenu moguće detekcije nosioca genetičkog opterećenja, prenatalnog nalaza i predmet genetičkog savetovališta. Skrining novoro�����enčadi na slušna oštećenja dao je nedvosmisleno veliki učinak, od rane detekcije i tretmana, uz brzi napredak genetike slušnih oštećenja – svrsishodnijim pristupom, prekoncepcijskoj i prenatalnoj dijagnostici, promenom kliničkog pristupa u obradi i lečenju tih oštećenja.Development of hearing apparatus is very complex process dependent on genome program, i.e. genetic instructions for anatomical and functional structuring of hearing sense and environmental factors, both of which enable and direct it through embriological, fetal, and postnatal period. Defects or deficiencies, and harmful consequences of one and/or both, are evident in hearing impairment. The most comon causes are genome and genetic structure of an individual. It is estimated that over 50% of all hearing losses are substantially genetical. Hearing impairment, being the most common sensorial disorder, is genetically very heterogenous. Mapping and identification of genes with specific roles in the development of structures and functions of this sense, when tested with DNA analysis, with direct or indirect mutation detection – point out the link between defect and impairment. Many hundreds of genes were discovered in the mechanism of development of hearing apparatus and its function. Some are responsible for clearly recognized components of structure and function of the sense, others – through encoded proteins act together in modifications, synthesis of regulators of other gene transcriptions, growth factors, etc. Furthermore, some genes were identified which cause dominant and recessive forms of syndrome and/or nonsyndrome deafness, which is in the domain of possible detection of carrier of genetic predisposition, prenatal positive finding and the subject of genetic counseling. Screening of newborns for hearing impairment has brought a great deal, from early detection and treatment, along with fast improvement of genetics in hearing impairment – with more appropriate approach, preconceptual and prenatal diagnostics, and changes in clinical approach in treatment of those impairments

Supplementary data for the article: Živković, J. M.; Stanković, I. M.; Ninković, D.; Zarić, S. D. Phenol and Toluene Stacking Interactions, Including Interactions at Large Horizontal Displacements. Study of Crystal Structures and Calculation of Potential Energy Surfaces. Crystal Growth & Design 2020, 20 (2), 1025–1034. https://doi.org/10.1021/acs.cgd.9b01353

Supplementary material for: [https://pubs.acs.org/doi/10.1021/acs.cgd.9b01353]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3973

Influence of hereditary elements on stuttering appearance

Naučnici danas podržavaju gledište da naslednost igra važnu ulogu u pojavi mucanja. Većina njih veruje da postoji predispozicija za pojavu mucanja, koja može da dovede neku decu pod veći rizik za ispoljavanje ovog govornog poremećaja. Rezultati iz našeg istraživanja, dobijeni na uzorku od 80 dece školskog uzrasta koja mucaju, kao i njihova analiza, pokazuju da postoji povezanost između pojave mucanja i postojanja mucanja u porodicama, kod dece u čijim porodicama postoji porodično opterećenje. Naime, pojava mucanja je znatno učestalija kod dece u čijim porodicama postoje članovi koji mucaju ili su nekada mucali. Takođe zapažamo da se mucanje češće javlja kod dece u čijim porodicama postoje članovi sa drugim, različitim poremećajima ritma i tempa govora. Utvrdili smo da ne postoji značajna povezanost pojave mucanja kod dece u čijim porodicama postoje članovi sa zakasnelim govornojezičkim razvojem. Navedeni podaci i zaključci dobijeni na osnovu ovog istraživanja, navode na eventualnu povezanost mucanja i nasledstva.Scientist today uphold a view that hereditary play important role in stuttering. Most of them belive that predisposition for stuttering phenomenon existe, and it can bring some children to higher risk for manifestation of this speech disorder. Research resultates, we have got from sample of 80 school age children with stuutering, as well as their analyses, show that correlation between appearence of stuttering and stuttering existe in families, at children from families where ballast existe. Particulary, stattering appearence is more frequent in families with other members who stutter too, or who stutter before. Moreover, we note that stuttering is more often in children within families where are a members with other, different fluent disorders. We find out that there no significante correlation bettwen stattering appearence in children within families where are a members with speech-language delay. Stated datas and conclutions we have got from this research, indicate on possibly correlation between stuttering and inheritance

Influence of hereditary elements on stuttering appearance

Naučnici danas podržavaju gledište da naslednost igra važnu ulogu u pojavi mucanja. Većina njih veruje da postoji predispozicija za pojavu mucanja, koja može da dovede neku decu pod veći rizik za ispoljavanje ovog govornog poremećaja. Rezultati iz našeg istraživanja, dobijeni na uzorku od 80 dece školskog uzrasta koja mucaju, kao i njihova analiza, pokazuju da postoji povezanost između pojave mucanja i postojanja mucanja u porodicama, kod dece u čijim porodicama postoji porodično opterećenje. Naime, pojava mucanja je znatno učestalija kod dece u čijim porodicama postoje članovi koji mucaju ili su nekada mucali. Takođe zapažamo da se mucanje češće javlja kod dece u čijim porodicama postoje članovi sa drugim, različitim poremećajima ritma i tempa govora. Utvrdili smo da ne postoji značajna povezanost pojave mucanja kod dece u čijim porodicama postoje članovi sa zakasnelim govornojezičkim razvojem. Navedeni podaci i zaključci dobijeni na osnovu ovog istraživanja, navode na eventualnu povezanost mucanja i nasledstva.Scientist today uphold a view that hereditary play important role in stuttering. Most of them belive that predisposition for stuttering phenomenon existe, and it can bring some children to higher risk for manifestation of this speech disorder. Research resultates, we have got from sample of 80 school age children with stuutering, as well as their analyses, show that correlation between appearence of stuttering and stuttering existe in families, at children from families where ballast existe. Particulary, stattering appearence is more frequent in families with other members who stutter too, or who stutter before. Moreover, we note that stuttering is more often in children within families where are a members with other, different fluent disorders. We find out that there no significante correlation bettwen stattering appearence in children within families where are a members with speech-language delay. Stated datas and conclutions we have got from this research, indicate on possibly correlation between stuttering and inheritance

Supplementary data for article: Vojislavljević-Vasilev, D.; Janjić, G. V.; Ninković, D.; Kapor, A.; Zarić, S. The Influence of Water Molecule Coordination onto the Water-Aromatic Interaction. Strong Interactions of Water Coordinating to a Metal Ion. CrystEngComm 2013, 15 (11), 2099–2105. https://doi.org/10.1039/c2ce25621e

Supplementary material for: [https://doi.org/10.1039/c2ce25621e]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1602

Supplementary data for article: Malenov, D. P.; Ninkovic, D. B.; Zaric, S. D. Stacking of Metal Chelates with Benzene: Can Dispersion-Corrected DFT Be Used to Calculate Organic-Inorganic Stacking? ChemPhysChem 2015, 16 (4), 761–768. https://doi.org/10.1002/cphc.201402589

Supporting information for: [https://doi.org/10.1002/cphc.201402589]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1675

Risk factors for Down syndrome

Daunov sindrom (DS) je najčešća hromozomska anomalija čoveka. Do sada jedini dokazani faktor rizika za DS kod deteta su godine života majke. U 90% slučajeva klasične trizomije 21 hromozomsko nerazdvajanje odigra se tokom oogeneze. Kod nekih majki dece sa DS na�����en je visok titar antitiroidnih antitela pa je moguće da autoimune bolesti majke doprinose hromozomskom nerazdvajanju. U nekim porodicama uočena je sklonost kod majki i njihovih baka ka hromozomskom nerazdvajanju, što ukazuje na mogućnost citoplazmatskog nasle�����ivanja predispozicije za trizomiju 21. Tako�����e, ovarijalni ćelijski mozaicizam sa trizomijom 21 dokumentovan je kod majki sa jednim ili više dece sa Daunovim sindromom. Naše istraživanje obuhvatilo je za 5 godina, 76 slučajeva dece sa citogenetski potvr�����enim DS, od toga 30 živoro�����enih i 46 indukovanih pobačaja. Na osnovu sačinjenog upitnika praćen je veći broj parametara na osnovu kojih smo analizirali moguće faktore rizika koji ukazuju na Daunov sindrom kod ploda. Rezultati pokazuju da je u 94,7% slučajeva Daunov sindroma razlog bila klasična trizomija 21, i da majke mla�����e od 35 godina učestvuju sa 73,4% u populaciji živoro�����ene dece sa DS. Prisutna je povezanost broja prethodnih trudnoća i spontanih pobačaja sa većim rizikom za DS kod ploda. Najčešća indikacija za prenatalnu dijagnozu bile su godine života majke. Nedelja gestacije u kojoj je postavljena dijagnoza DS kod ploda bila je u proseku izme�����u 23. i 35., što ima za posledicu prekid trudnoće kasnije kada je rizik veći. Daunov sindrom kod nas i dalje ostaje aktuelan društveni, psihološki, sociološki, kao i značajan problem porodice sa decom sa Daunov sindromom.Down syndrome (DS) is the most common chromosome anomaly in humans. The only risk factor for DS proven so far is the maternal age. In 90% of classic trisomy 21 chromosomal nondisjunction takes place during oogenesis. Some mothers of DS children were found to have high antithyroid titers so one would assume that mother’s autoimmune diseases contribute to chromosomal nondisjunction. Within some families there is the tendency in mothers and their grandmothers towards chromosomal nondisjunction, which brings out the possibility of cytoplasmatic inheritance of predilection for trisomy 21. Furthermore, ovarian cellular mosaicism with trisomy 21 was documented in mothers with 1 or more children with Down syndrome. During 5 years we investigated 76 children with cytogenetically proven DS, 30 of those being liveborn, and 46 with induced abortion. The special questionnaire was made to monitor many parameters by which we analysed possible risk factors which suggest Down syndrome in fetus. The results show that classic trisomy 21 was in 94,7% cases, and that mothers younger than 35 years of age make 73,4% in the population of liveborn children with DS. There is a correlation between previous pregnancies and spontaneous miscarriages with a higher risk for DS in a fetus. The most common indication for prenatal diagnosis was maternal age. The mean week of gestation when the diagnosis of DS was made was 23-35, which meant that pregnancies were terminated later when the risk is higher. In our country Down syndrome remains acute social, psychological, sociological as well as important problem for families with DS children

Supplementary data for the article: Ninković, D. B.; Vojislavljević-Vasilev, D. Z.; Medaković, V. B.; Hall, M. B.; Brothers, E. N.; Zarić, S. D. Aliphatic-Aromatic Stacking Interactions in Cyclohexane-Benzene Are Stronger than Aromatic-Aromatic Interaction in the Benzene Dimer. Physical Chemistry Chemical Physics 2016, 18 (37), 25791–25795. https://doi.org/10.1039/c6cp03734h

Supplementary material for: [https://doi.org/10.1039/c6cp03734h]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2328]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3324

Risk factors for Down syndrome

Daunov sindrom (DS) je najčešća hromozomska anomalija čoveka. Do sada jedini dokazani faktor rizika za DS kod deteta su godine života majke. U 90% slučajeva klasične trizomije 21 hromozomsko nerazdvajanje odigra se tokom oogeneze. Kod nekih majki dece sa DS na�����en je visok titar antitiroidnih antitela pa je moguće da autoimune bolesti majke doprinose hromozomskom nerazdvajanju. U nekim porodicama uočena je sklonost kod majki i njihovih baka ka hromozomskom nerazdvajanju, što ukazuje na mogućnost citoplazmatskog nasle�����ivanja predispozicije za trizomiju 21. Tako�����e, ovarijalni ćelijski mozaicizam sa trizomijom 21 dokumentovan je kod majki sa jednim ili više dece sa Daunovim sindromom. Naše istraživanje obuhvatilo je za 5 godina, 76 slučajeva dece sa citogenetski potvr�����enim DS, od toga 30 živoro�����enih i 46 indukovanih pobačaja. Na osnovu sačinjenog upitnika praćen je veći broj parametara na osnovu kojih smo analizirali moguće faktore rizika koji ukazuju na Daunov sindrom kod ploda. Rezultati pokazuju da je u 94,7% slučajeva Daunov sindroma razlog bila klasična trizomija 21, i da majke mla�����e od 35 godina učestvuju sa 73,4% u populaciji živoro�����ene dece sa DS. Prisutna je povezanost broja prethodnih trudnoća i spontanih pobačaja sa većim rizikom za DS kod ploda. Najčešća indikacija za prenatalnu dijagnozu bile su godine života majke. Nedelja gestacije u kojoj je postavljena dijagnoza DS kod ploda bila je u proseku izme�����u 23. i 35., što ima za posledicu prekid trudnoće kasnije kada je rizik veći. Daunov sindrom kod nas i dalje ostaje aktuelan društveni, psihološki, sociološki, kao i značajan problem porodice sa decom sa Daunov sindromom.Down syndrome (DS) is the most common chromosome anomaly in humans. The only risk factor for DS proven so far is the maternal age. In 90% of classic trisomy 21 chromosomal nondisjunction takes place during oogenesis. Some mothers of DS children were found to have high antithyroid titers so one would assume that mother’s autoimmune diseases contribute to chromosomal nondisjunction. Within some families there is the tendency in mothers and their grandmothers towards chromosomal nondisjunction, which brings out the possibility of cytoplasmatic inheritance of predilection for trisomy 21. Furthermore, ovarian cellular mosaicism with trisomy 21 was documented in mothers with 1 or more children with Down syndrome. During 5 years we investigated 76 children with cytogenetically proven DS, 30 of those being liveborn, and 46 with induced abortion. The special questionnaire was made to monitor many parameters by which we analysed possible risk factors which suggest Down syndrome in fetus. The results show that classic trisomy 21 was in 94,7% cases, and that mothers younger than 35 years of age make 73,4% in the population of liveborn children with DS. There is a correlation between previous pregnancies and spontaneous miscarriages with a higher risk for DS in a fetus. The most common indication for prenatal diagnosis was maternal age. The mean week of gestation when the diagnosis of DS was made was 23-35, which meant that pregnancies were terminated later when the risk is higher. In our country Down syndrome remains acute social, psychological, sociological as well as important problem for families with DS children