TY  - JOUR
AU  - Maksić, Jasmina
AU  - Maksimović, Nela
AU  - Rasulić, Lukas
AU  - Milankov, Olgica
AU  - Marjanović, Ana
AU  - Cvetković, Dragana
AU  - Rakočević Stojanović, Vidosava
AU  - Novaković, Ivana
PY  - 2023
UR  - http://rfasper.fasper.bg.ac.rs/handle/123456789/5288
AB  - Background/Aim. Duchenne muscular dystrophy (MD) and Becker MD are caused by mutations in the gene for dystrophin (DMD). They are X chromosome-linked reces-sive diseases where males are affected, and females are healthy carriers of the mutation in most cases. It is estimat-ed that 2/3 of mothers of Duchenne MD probands are car-riers, while 1/3 of probands have de novo mutations. The aim of the study was to confirm the carrier status of female members of the families of Duchenne MD/Becker MD probands using direct genetic testing methods. Methods. The study included 38 females from 31 families of Du-chenne MD/Becker MD probands with dele-tion/duplication in the DMD gene. Moreover, 4 cases of prenatal diagnosis of Duchenne MD/Becker MD were in-cluded. The methods of polymerase chain reaction - PCR and the multiplex ligation-dependent probe amplification - MLPA were applied for detecting deletions, i.e., dele-tion/duplication mutations in the DMD gene. Results. In the total of 31 Duchenne MD/Becker MD probands, 87.1% of deletions and 12.9% of duplications of one or more exons in the DMD gene were detected. Of the 29 tested mothers, mutations were found in 17 of them (14 de-letions and 3 duplications). Mutations were detected in 11 (57.9%) out of 19 mothers of probands with the Duchenne MD phenotype and 6 (60%) out of 10 mothers of Becker MD probands. Furthermore, 14 (56%) out of 25 mothers were carriers in probands with deletions, and 3 (75%) out of 4 mothers were carriers in probands with duplications. In the remaining 9 other female relatives of the patients, muta-tions were found in 4. In prenatal diagnosis, we identified a deletion in one male and one female fetus of one single mother who was confirmed as a carrier. Conclusion. The study showed that mothers were carriers in almost 60% of sporadic cases of Duchenne MD/Becker MD with dele-tions and duplications. In addition, the carrier frequency tended to be higher in mothers of the probands with dupli-cations (75%) compared to mothers of probands with dele-tions (56%).
AB  - Uvod/Cilj. Dišenova mišićna distrofija (MD) i Bekerova MD su uzrokovane mutacijama u genu za distrofin (DMD). To su recesivne bolesti vezane za X hromozom, od kojih obolevaju muškarci, a žene su uglavnom zdravi nosioci mu-tacije. Procenjeno je da su kod probanada obolelih od Dišenove MD 2/3 majki nosioci mutacije, dok 1/3 pro-banada ima de novo mutaciju. Cilj rada bio je da se potvrdi status nosioca mutacije kod ženskih članova porodica pro-banada obolelih od Dišenove MD/Bekerove MD primenom metoda direktnog genetičkog testiranja. Metode. Studija je obuhvatila ukupno 38 žena iz 31 porodice pro-banada obolelih od Dišenove MD/Bekerove MD sa deleci-jom/duplikacijom u DMD genu. Takođe, u studiju su bila uključena i 4 slučaja Dišenove MD/Bekerove MD otkrivena prenatalnom dijagnostikom. Metoda lančane reakcije poli-meraze (polymerase chain reaction – PCR) i metoda višestrukog umnožavanja vezanih proba (multiplex ligation-dependent probe amplification -MLPA) su korišćene za detekciju delecija, od-nosno delecija/duplikacija mutacija u DMD genu. Rezulta-ti. Kod ukupno 31 probanada obolelih od Dišenove MD/Bekerove MD, utvrđeno je 87,1% mutacija tipa deleci-je i 12,9% mutacija tipa duplikacija jednog ili više egzona u DMD genu. Od 29 testiranih majki probanada, mutacije su nađene kod njih 17 (14 delecija i 3 duplikacije). Mutacije su detektovane kod 11 (57,9%) od 19 majki probanada sa feno-tipom Dišenove MD i kod 6 (60%) od 10 majki probanada obolelih od Bekerove MD. Takođe, kod probanada sa de-lecijom, kod 14 (56%) od 25 majki je potvrđeno da su nosioci mutacije, a kod probanada sa duplikacijom, 3 (75%) od 4 majke su bile nosioci mutacije. Od ostalih 9 ženskih srodnika probanada obolelih od Dišenove MD/Bekerove MD, mutacije su nađene kod nijh 4. Prenatalnom dijagnos tikom utvrđene su delecije kod jednog muškog i jednog ženskog fetusa iste majke koja je bila potvrđena kao nosilac mutacije. Zaključak. Istraživanje je pokazalo da su majke bile nosioci mutacija u skoro 60% izolovanih slučajeva ob-olelih od Dišenove MD/Bekerove MD sa delecijama i duplikacijama. Takođe, učestalost majki nosioca mutacije kod probanada sa duplikaciom (75%) se pokazala višom ne-go kod majki probanada sa delecijom (56%).
PB  - Vojnomedicinska akademija
T2  - Vojnosanitetski pregled
T1  - The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies
T1  - Značaj direktnog genetičkog testiranja za otkrivanje žena prenosioca mutacije kod distrofinopatija
EP  - 207
IS  - 3
SP  - 201
VL  - 80
DO  - 10.2298/VSP190208030M
ER  - 

@article{
author = "Maksić, Jasmina and Maksimović, Nela and Rasulić, Lukas and Milankov, Olgica and Marjanović, Ana and Cvetković, Dragana and Rakočević Stojanović, Vidosava and Novaković, Ivana",
year = "2023",
abstract = "Background/Aim. Duchenne muscular dystrophy (MD) and Becker MD are caused by mutations in the gene for dystrophin (DMD). They are X chromosome-linked reces-sive diseases where males are affected, and females are healthy carriers of the mutation in most cases. It is estimat-ed that 2/3 of mothers of Duchenne MD probands are car-riers, while 1/3 of probands have de novo mutations. The aim of the study was to confirm the carrier status of female members of the families of Duchenne MD/Becker MD probands using direct genetic testing methods. Methods. The study included 38 females from 31 families of Du-chenne MD/Becker MD probands with dele-tion/duplication in the DMD gene. Moreover, 4 cases of prenatal diagnosis of Duchenne MD/Becker MD were in-cluded. The methods of polymerase chain reaction - PCR and the multiplex ligation-dependent probe amplification - MLPA were applied for detecting deletions, i.e., dele-tion/duplication mutations in the DMD gene. Results. In the total of 31 Duchenne MD/Becker MD probands, 87.1% of deletions and 12.9% of duplications of one or more exons in the DMD gene were detected. Of the 29 tested mothers, mutations were found in 17 of them (14 de-letions and 3 duplications). Mutations were detected in 11 (57.9%) out of 19 mothers of probands with the Duchenne MD phenotype and 6 (60%) out of 10 mothers of Becker MD probands. Furthermore, 14 (56%) out of 25 mothers were carriers in probands with deletions, and 3 (75%) out of 4 mothers were carriers in probands with duplications. In the remaining 9 other female relatives of the patients, muta-tions were found in 4. In prenatal diagnosis, we identified a deletion in one male and one female fetus of one single mother who was confirmed as a carrier. Conclusion. The study showed that mothers were carriers in almost 60% of sporadic cases of Duchenne MD/Becker MD with dele-tions and duplications. In addition, the carrier frequency tended to be higher in mothers of the probands with dupli-cations (75%) compared to mothers of probands with dele-tions (56%)., Uvod/Cilj. Dišenova mišićna distrofija (MD) i Bekerova MD su uzrokovane mutacijama u genu za distrofin (DMD). To su recesivne bolesti vezane za X hromozom, od kojih obolevaju muškarci, a žene su uglavnom zdravi nosioci mu-tacije. Procenjeno je da su kod probanada obolelih od Dišenove MD 2/3 majki nosioci mutacije, dok 1/3 pro-banada ima de novo mutaciju. Cilj rada bio je da se potvrdi status nosioca mutacije kod ženskih članova porodica pro-banada obolelih od Dišenove MD/Bekerove MD primenom metoda direktnog genetičkog testiranja. Metode. Studija je obuhvatila ukupno 38 žena iz 31 porodice pro-banada obolelih od Dišenove MD/Bekerove MD sa deleci-jom/duplikacijom u DMD genu. Takođe, u studiju su bila uključena i 4 slučaja Dišenove MD/Bekerove MD otkrivena prenatalnom dijagnostikom. Metoda lančane reakcije poli-meraze (polymerase chain reaction – PCR) i metoda višestrukog umnožavanja vezanih proba (multiplex ligation-dependent probe amplification -MLPA) su korišćene za detekciju delecija, od-nosno delecija/duplikacija mutacija u DMD genu. Rezulta-ti. Kod ukupno 31 probanada obolelih od Dišenove MD/Bekerove MD, utvrđeno je 87,1% mutacija tipa deleci-je i 12,9% mutacija tipa duplikacija jednog ili više egzona u DMD genu. Od 29 testiranih majki probanada, mutacije su nađene kod njih 17 (14 delecija i 3 duplikacije). Mutacije su detektovane kod 11 (57,9%) od 19 majki probanada sa feno-tipom Dišenove MD i kod 6 (60%) od 10 majki probanada obolelih od Bekerove MD. Takođe, kod probanada sa de-lecijom, kod 14 (56%) od 25 majki je potvrđeno da su nosioci mutacije, a kod probanada sa duplikacijom, 3 (75%) od 4 majke su bile nosioci mutacije. Od ostalih 9 ženskih srodnika probanada obolelih od Dišenove MD/Bekerove MD, mutacije su nađene kod nijh 4. Prenatalnom dijagnos tikom utvrđene su delecije kod jednog muškog i jednog ženskog fetusa iste majke koja je bila potvrđena kao nosilac mutacije. Zaključak. Istraživanje je pokazalo da su majke bile nosioci mutacija u skoro 60% izolovanih slučajeva ob-olelih od Dišenove MD/Bekerove MD sa delecijama i duplikacijama. Takođe, učestalost majki nosioca mutacije kod probanada sa duplikaciom (75%) se pokazala višom ne-go kod majki probanada sa delecijom (56%).",
publisher = "Vojnomedicinska akademija",
journal = "Vojnosanitetski pregled",
title = "The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies, Značaj direktnog genetičkog testiranja za otkrivanje žena prenosioca mutacije kod distrofinopatija",
pages = "207-201",
number = "3",
volume = "80",
doi = "10.2298/VSP190208030M"
}

Maksić, J., Maksimović, N., Rasulić, L., Milankov, O., Marjanović, A., Cvetković, D., Rakočević Stojanović, V.,& Novaković, I.. (2023). The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies. in Vojnosanitetski pregled
Vojnomedicinska akademija., 80(3), 201-207.
https://doi.org/10.2298/VSP190208030M

Maksić J, Maksimović N, Rasulić L, Milankov O, Marjanović A, Cvetković D, Rakočević Stojanović V, Novaković I. The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies. in Vojnosanitetski pregled. 2023;80(3):201-207.
doi:10.2298/VSP190208030M .

Maksić, Jasmina, Maksimović, Nela, Rasulić, Lukas, Milankov, Olgica, Marjanović, Ana, Cvetković, Dragana, Rakočević Stojanović, Vidosava, Novaković, Ivana, "The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies" in Vojnosanitetski pregled, 80, no. 3 (2023):201-207,
https://doi.org/10.2298/VSP190208030M . .

TY  - JOUR
AU  - Maksić, Jasmina
AU  - Maksimović, Nela
AU  - Rasulić, Lukas
AU  - Milankov, Olgica
AU  - Marjanović, Ana
AU  - Cvetković, Dragana
AU  - Rakočević, Vidosava
AU  - Rakočević  Stojanović, Vidosava
AU  - Novaković, Ivana
PY  - 2023
UR  - http://rfasper.fasper.bg.ac.rs/handle/123456789/4756
AB  - Duchenne muscular dystrophy (DMD) and Becker muscular
dystrophy (BMD) are caused by mutations in the dystrophin gene. They are X-linked
recessive diseases, where males are affected and females are mostly healthy carriers of the
mutation. It is estimated that 2/3 mothers of DMD probands are carriers, while 1/3 of
patients have de novo mutations. The aim was to confirm the carrier status of females in the
families of DMD/BMD probands, using direct genetic methods. Methods. We tested 38
females from 31 families of DMD/BMD probands with deletion/duplication in the
dystrophin gene. Also, 4 cases of prenatal diagnosis of DMD/BMD were included. We
preformed the polymerase chain reaction (PCR) and the multiplex ligation-dependent
method (MLPA) for deletion detection, i.e. deletion/duplication in the dystrophin gene.
Results. In 31 DMD/BMD probands, we identified 87.1% deletions and 12.9%
duplications of one or more exons. Of the 29 tested mothers, mutations were found in 17
(14 deletions and 3 duplications). Mutations were found in 57.9% (11/19) mothers of DMD
and in 60% (6/10) mothers of BMD, respectively. Also, in probands with deletions 56%
(14/25) of mothers were carries and in probands with duplications 3 mothers of 4 (75%).
Of the 9 other female relatives, mutations were found in 4. In prenatal diagnosis, we
identified deletion in one male and one female foetus of one mother. Conclusion. The
study showed that mothers were carriers in almost 60% of sporadic cases of DMD/BMD
with deletions and duplication. Also, the carrier frequency tended to be higher in mothers
of the probands with duplication (75%) then in probands with deletions (56%). In the case
of a mother who was confirmed as a carrier, deletion was detected in 2 of 3 foetuses.
AB  - Dišenova mišićna distrofija (DMD) i Bekerova mišićna distrofija (BMD) su
uzrokovane mutacijama u genu za distrofin. To su X-vezane recesivne bolesti, gde
oboljevaju muškarci a žene su uglavnom zdravi prenosioci mutacije. Procenjeno je da su
kod DMD probanada 2/3 majki nosioci, dok 1/3 pacijenata ima novu mutaciju. Cilj rada je
bio da se utvrdi status prenosioca kod žena u porodicama obolelih od DMD/BMD,
primenom direktne genetičke metode. Metode. Testirali smo 38 žena iz 31 porodice
DMD/BMD probanada sa delecijama i duplikacijama u genu za distrofin. Takođe, u studiju
su bila uključena i 4 slučaja prenatalne DMD/BMD dijagnoze. Primenjene su metoda
lančane reakcije polimerizacije (PCR) i metoda višestrukog umnožavanja vezanih proba
(MLPA) za detekciju delecija, odnosno delecija i duplikacija u genu za distrofin. Rezultati.
Kod 31-og DMD/BMD probanda utvrđeno je 87,1% delecija i 12,9% duplikacija jednog ili
više egzona. Od 29 testiranih majki probanada, mutacije su nađene kod njih 17 (14 delecija
i 3 duplikacije). Mutacije su nađene kod 57,9% (11/19) majki probanada sa DMD
fenotipom i kod 60% majki probanada sa BMD. Takođe, kod probanada sa delecijom 56%
(14/25) majki su potvrđene kao nosioci, a kod probanada sa duplikacijom 3 od 4 majke
(75%). Od preostalih 9 ženskih srodnika, mutacije su nađene kod nijh 4. Prenatalnom
dijagnostikom utvrđene su delecije kod jednog muškog i jednog ženskog ploda iste majke.
Zaključak. Istraživanje je pokazalo da su majke bile nosioci u skoro 60% izolovanih
DMD/BMD slučajeva sa delecijama i duplikacijama. Takođe, učestalost majki nosioca kod
probanada sa duplikaciom (75%) se pokazala većom nego kod majki probanada sa
delecijom (56%). U slučaju majke koja je bila potvrđena kao nosilac, delecija je otkrivena
kod njena 2 ploda od 3 ispitana.
PB  - Vojnomedicinska akademija
T2  - Vojnosanitetski pregled
T1  - The importance of direct genetic testing to determine female carriers in dystrophinopathies
T1  - Značaj direktnog genetičkog testiranja za utvrđivanje žena prenosioca kod distrofinopatija
EP  - 207
IS  - 3
SP  - 201
VL  - 80
DO  - 10.2298/VSP190208030SM
ER  - 

@article{
author = "Maksić, Jasmina and Maksimović, Nela and Rasulić, Lukas and Milankov, Olgica and Marjanović, Ana and Cvetković, Dragana and Rakočević, Vidosava and Rakočević  Stojanović, Vidosava and Novaković, Ivana",
year = "2023",
abstract = "Duchenne muscular dystrophy (DMD) and Becker muscular
dystrophy (BMD) are caused by mutations in the dystrophin gene. They are X-linked
recessive diseases, where males are affected and females are mostly healthy carriers of the
mutation. It is estimated that 2/3 mothers of DMD probands are carriers, while 1/3 of
patients have de novo mutations. The aim was to confirm the carrier status of females in the
families of DMD/BMD probands, using direct genetic methods. Methods. We tested 38
females from 31 families of DMD/BMD probands with deletion/duplication in the
dystrophin gene. Also, 4 cases of prenatal diagnosis of DMD/BMD were included. We
preformed the polymerase chain reaction (PCR) and the multiplex ligation-dependent
method (MLPA) for deletion detection, i.e. deletion/duplication in the dystrophin gene.
Results. In 31 DMD/BMD probands, we identified 87.1% deletions and 12.9%
duplications of one or more exons. Of the 29 tested mothers, mutations were found in 17
(14 deletions and 3 duplications). Mutations were found in 57.9% (11/19) mothers of DMD
and in 60% (6/10) mothers of BMD, respectively. Also, in probands with deletions 56%
(14/25) of mothers were carries and in probands with duplications 3 mothers of 4 (75%).
Of the 9 other female relatives, mutations were found in 4. In prenatal diagnosis, we
identified deletion in one male and one female foetus of one mother. Conclusion. The
study showed that mothers were carriers in almost 60% of sporadic cases of DMD/BMD
with deletions and duplication. Also, the carrier frequency tended to be higher in mothers
of the probands with duplication (75%) then in probands with deletions (56%). In the case
of a mother who was confirmed as a carrier, deletion was detected in 2 of 3 foetuses., Dišenova mišićna distrofija (DMD) i Bekerova mišićna distrofija (BMD) su
uzrokovane mutacijama u genu za distrofin. To su X-vezane recesivne bolesti, gde
oboljevaju muškarci a žene su uglavnom zdravi prenosioci mutacije. Procenjeno je da su
kod DMD probanada 2/3 majki nosioci, dok 1/3 pacijenata ima novu mutaciju. Cilj rada je
bio da se utvrdi status prenosioca kod žena u porodicama obolelih od DMD/BMD,
primenom direktne genetičke metode. Metode. Testirali smo 38 žena iz 31 porodice
DMD/BMD probanada sa delecijama i duplikacijama u genu za distrofin. Takođe, u studiju
su bila uključena i 4 slučaja prenatalne DMD/BMD dijagnoze. Primenjene su metoda
lančane reakcije polimerizacije (PCR) i metoda višestrukog umnožavanja vezanih proba
(MLPA) za detekciju delecija, odnosno delecija i duplikacija u genu za distrofin. Rezultati.
Kod 31-og DMD/BMD probanda utvrđeno je 87,1% delecija i 12,9% duplikacija jednog ili
više egzona. Od 29 testiranih majki probanada, mutacije su nađene kod njih 17 (14 delecija
i 3 duplikacije). Mutacije su nađene kod 57,9% (11/19) majki probanada sa DMD
fenotipom i kod 60% majki probanada sa BMD. Takođe, kod probanada sa delecijom 56%
(14/25) majki su potvrđene kao nosioci, a kod probanada sa duplikacijom 3 od 4 majke
(75%). Od preostalih 9 ženskih srodnika, mutacije su nađene kod nijh 4. Prenatalnom
dijagnostikom utvrđene su delecije kod jednog muškog i jednog ženskog ploda iste majke.
Zaključak. Istraživanje je pokazalo da su majke bile nosioci u skoro 60% izolovanih
DMD/BMD slučajeva sa delecijama i duplikacijama. Takođe, učestalost majki nosioca kod
probanada sa duplikaciom (75%) se pokazala većom nego kod majki probanada sa
delecijom (56%). U slučaju majke koja je bila potvrđena kao nosilac, delecija je otkrivena
kod njena 2 ploda od 3 ispitana.",
publisher = "Vojnomedicinska akademija",
journal = "Vojnosanitetski pregled",
title = "The importance of direct genetic testing to determine female carriers in dystrophinopathies, Značaj direktnog genetičkog testiranja za utvrđivanje žena prenosioca kod distrofinopatija",
pages = "207-201",
number = "3",
volume = "80",
doi = "10.2298/VSP190208030SM"
}

Maksić, J., Maksimović, N., Rasulić, L., Milankov, O., Marjanović, A., Cvetković, D., Rakočević, V., Rakočević  Stojanović, V.,& Novaković, I.. (2023). The importance of direct genetic testing to determine female carriers in dystrophinopathies. in Vojnosanitetski pregled
Vojnomedicinska akademija., 80(3), 201-207.
https://doi.org/10.2298/VSP190208030SM

Maksić J, Maksimović N, Rasulić L, Milankov O, Marjanović A, Cvetković D, Rakočević V, Rakočević  Stojanović V, Novaković I. The importance of direct genetic testing to determine female carriers in dystrophinopathies. in Vojnosanitetski pregled. 2023;80(3):201-207.
doi:10.2298/VSP190208030SM .

Maksić, Jasmina, Maksimović, Nela, Rasulić, Lukas, Milankov, Olgica, Marjanović, Ana, Cvetković, Dragana, Rakočević, Vidosava, Rakočević  Stojanović, Vidosava, Novaković, Ivana, "The importance of direct genetic testing to determine female carriers in dystrophinopathies" in Vojnosanitetski pregled, 80, no. 3 (2023):201-207,
https://doi.org/10.2298/VSP190208030SM . .

TY  - JOUR
AU  - Maksić, Jasmina
AU  - Dobričić, Valerija
AU  - Rasulić, Lukas
AU  - Maksimović, Nela
AU  - Branković, Marija
AU  - Milić-Rašić, Vedrana
AU  - Rakočević-Stojanović, Vidosava
AU  - Novaković, Ivana
PY  - 2020
UR  - http://rfasper.fasper.bg.ac.rs/handle/123456789/1261
AB  - Background/Aim. Duchenne muscular dystrophy (DMD) and its allelic form Becker muscular dystrophy (BMD) are X-linked diseases that affect males, characterized by progressive muscle and cardiopulmonary weakness, especially in DMD as a severe form of the disease. They result from mutations in the dystrophin gene, and the most common changes are large intragenic deletions and duplications (80%). One third of patients have de novo mutation and 2/3 of the mothers are estimated as carriers. The aim of the study was to analyze the frequency of duplications versus deletions in the dystrophin gene in patients with dystrophinopathies, as well as to analyze the phenotypic effect of large mutations obtained and to determine the carrier status of female relatives in probands with duplications. Methods. We examined 22 DMD and 35 BMD unrelated patients and 6 female relatives of the probands where duplications were found. We used polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) methods, according to the protocol, to detect or confirm mutations in probands and female carriers. Results. In probands, there were 34 (59.6%) large deletions (mostly affected exons 44-60) and 6 (10.5%) large duplications in 4 DMD and 2 BMD patients. Also, duplications were found in 3 out of 4 (75%) tested mothers. The distribution of duplications was heterogeneous, affecting N-terminal and central rod domain, and included more exons, except for one DMD patient who had duplication of exon 2. An exception from the Monaco rule was present in 9.5% of DMD and 15.8% of BMD probands, i.e. in 12.5% of DMD/BMD cases. Conclusion. In 57 DMD/BMD probands, we found 59.6% of large deletions and 10.5% of large duplications. The most affected region of the DMD gene was the central rod domain. An exception to Monaco's rule was present in 12.5% of DMD/BMD cases. Three out of 4 examined proband's mothers were confirmed as carriers.
AB  - Uvod/Cilj. Dišenova mišićna distrofija (DMD) i njegova alelna forma, Bekerova mišićna distrofija (BMD), su Xvezane nasledne bolesti od kojih obolevaju muškarci, a karakteriše ih progresivna mišićna i kardiopulmonalna slabost, posebno kod DMD kao težeg oblika bolesti. Ove bolesti nastaju kao posledica mutacija u genu za distrofin, a najčešće su prisutne intragenske delecije i duplikacije (80%). Novonastalu mutaciju ima1/3 bolesnika, a procenjeno je da su 2/3 majki nosioci. Cilj rada je bio da se analizira učestalost duplikacija u odnosu na delecije u genu za distrofin kod bolesnika sa distrofinopatijom, kao i da se ispita efekat dobijenih mutacija na fenotip kod probanda i utvrdimo status nosioca kod ženskih srodnika probanda sa duplikacijama. Metode. Studijom je bilo obuhvaćeno 22 DMD i 35 BMD nesrodnih bolesnika i šest ženskih srodnika probanda kod kojih su bile otkrivene duplikacije. Za otkrivanje ili potvrdu mutacije, kod probanda i ženskih nosioca, korišćene su metode: lančana reakcija polimerazom (PCR) i višestruko umnožavanje vezanih sondi (MLPA), prema datom protokolu. Rezultati. Kod probanda je nađeno 34 (59,6%) velikih delecija (najčešće su bili zahvaćeni egzoni 44-60) i 6 velikih duplikacija (10,5%) kod 4 DMD i 2 BMD bolesnika. Takođe, duplikacije su nađene kod 3 od 4 (75%) testirane majke. Distribucija duplikacija je bila heterogena, obuhvatala je N-terminalni i štapićasti region i uključivala je veći broj egzona, osim kod jednog DMD bolesnika koji je imao duplikaciju egzona 2. Odstupanje od Monakovog pravila je bilo prisutno kod 9,5% DMD probanda, odnosno kod 15,8% BMD probanda, to jest kod 12,5% slučajeva. Zaključak. Kod 57 DMD/BMD probanda nađeno je 59,6% velikih delecija i 10,5% velikih duplikacija. Najčešće je bio zahvaćen štapićasti domen u DMD genu. Odstupanje od Monakovog pravila je bilo prisutno u 12,5% DMD/BMD slučajeva. Tri od četiri ispitane majke probanda su bile potvrđene kao nosioci.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Analysis of duplications versus deletions in the dystrophin gene in Serbian cohort with dystrophinopathies
T1  - Uporedna analiza duplikacija i delecija u genu za distrofin u grupi bolesnika sa distrofinopatijom iz Srbije
EP  - 394
IS  - 4
SP  - 387
VL  - 77
DO  - 10.2298/VSP180226089M
ER  - 

@article{
author = "Maksić, Jasmina and Dobričić, Valerija and Rasulić, Lukas and Maksimović, Nela and Branković, Marija and Milić-Rašić, Vedrana and Rakočević-Stojanović, Vidosava and Novaković, Ivana",
year = "2020",
abstract = "Background/Aim. Duchenne muscular dystrophy (DMD) and its allelic form Becker muscular dystrophy (BMD) are X-linked diseases that affect males, characterized by progressive muscle and cardiopulmonary weakness, especially in DMD as a severe form of the disease. They result from mutations in the dystrophin gene, and the most common changes are large intragenic deletions and duplications (80%). One third of patients have de novo mutation and 2/3 of the mothers are estimated as carriers. The aim of the study was to analyze the frequency of duplications versus deletions in the dystrophin gene in patients with dystrophinopathies, as well as to analyze the phenotypic effect of large mutations obtained and to determine the carrier status of female relatives in probands with duplications. Methods. We examined 22 DMD and 35 BMD unrelated patients and 6 female relatives of the probands where duplications were found. We used polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) methods, according to the protocol, to detect or confirm mutations in probands and female carriers. Results. In probands, there were 34 (59.6%) large deletions (mostly affected exons 44-60) and 6 (10.5%) large duplications in 4 DMD and 2 BMD patients. Also, duplications were found in 3 out of 4 (75%) tested mothers. The distribution of duplications was heterogeneous, affecting N-terminal and central rod domain, and included more exons, except for one DMD patient who had duplication of exon 2. An exception from the Monaco rule was present in 9.5% of DMD and 15.8% of BMD probands, i.e. in 12.5% of DMD/BMD cases. Conclusion. In 57 DMD/BMD probands, we found 59.6% of large deletions and 10.5% of large duplications. The most affected region of the DMD gene was the central rod domain. An exception to Monaco's rule was present in 12.5% of DMD/BMD cases. Three out of 4 examined proband's mothers were confirmed as carriers., Uvod/Cilj. Dišenova mišićna distrofija (DMD) i njegova alelna forma, Bekerova mišićna distrofija (BMD), su Xvezane nasledne bolesti od kojih obolevaju muškarci, a karakteriše ih progresivna mišićna i kardiopulmonalna slabost, posebno kod DMD kao težeg oblika bolesti. Ove bolesti nastaju kao posledica mutacija u genu za distrofin, a najčešće su prisutne intragenske delecije i duplikacije (80%). Novonastalu mutaciju ima1/3 bolesnika, a procenjeno je da su 2/3 majki nosioci. Cilj rada je bio da se analizira učestalost duplikacija u odnosu na delecije u genu za distrofin kod bolesnika sa distrofinopatijom, kao i da se ispita efekat dobijenih mutacija na fenotip kod probanda i utvrdimo status nosioca kod ženskih srodnika probanda sa duplikacijama. Metode. Studijom je bilo obuhvaćeno 22 DMD i 35 BMD nesrodnih bolesnika i šest ženskih srodnika probanda kod kojih su bile otkrivene duplikacije. Za otkrivanje ili potvrdu mutacije, kod probanda i ženskih nosioca, korišćene su metode: lančana reakcija polimerazom (PCR) i višestruko umnožavanje vezanih sondi (MLPA), prema datom protokolu. Rezultati. Kod probanda je nađeno 34 (59,6%) velikih delecija (najčešće su bili zahvaćeni egzoni 44-60) i 6 velikih duplikacija (10,5%) kod 4 DMD i 2 BMD bolesnika. Takođe, duplikacije su nađene kod 3 od 4 (75%) testirane majke. Distribucija duplikacija je bila heterogena, obuhvatala je N-terminalni i štapićasti region i uključivala je veći broj egzona, osim kod jednog DMD bolesnika koji je imao duplikaciju egzona 2. Odstupanje od Monakovog pravila je bilo prisutno kod 9,5% DMD probanda, odnosno kod 15,8% BMD probanda, to jest kod 12,5% slučajeva. Zaključak. Kod 57 DMD/BMD probanda nađeno je 59,6% velikih delecija i 10,5% velikih duplikacija. Najčešće je bio zahvaćen štapićasti domen u DMD genu. Odstupanje od Monakovog pravila je bilo prisutno u 12,5% DMD/BMD slučajeva. Tri od četiri ispitane majke probanda su bile potvrđene kao nosioci.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Analysis of duplications versus deletions in the dystrophin gene in Serbian cohort with dystrophinopathies, Uporedna analiza duplikacija i delecija u genu za distrofin u grupi bolesnika sa distrofinopatijom iz Srbije",
pages = "394-387",
number = "4",
volume = "77",
doi = "10.2298/VSP180226089M"
}

Maksić, J., Dobričić, V., Rasulić, L., Maksimović, N., Branković, M., Milić-Rašić, V., Rakočević-Stojanović, V.,& Novaković, I.. (2020). Analysis of duplications versus deletions in the dystrophin gene in Serbian cohort with dystrophinopathies. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 77(4), 387-394.
https://doi.org/10.2298/VSP180226089M

Maksić J, Dobričić V, Rasulić L, Maksimović N, Branković M, Milić-Rašić V, Rakočević-Stojanović V, Novaković I. Analysis of duplications versus deletions in the dystrophin gene in Serbian cohort with dystrophinopathies. in Vojnosanitetski pregled. 2020;77(4):387-394.
doi:10.2298/VSP180226089M .

Maksić, Jasmina, Dobričić, Valerija, Rasulić, Lukas, Maksimović, Nela, Branković, Marija, Milić-Rašić, Vedrana, Rakočević-Stojanović, Vidosava, Novaković, Ivana, "Analysis of duplications versus deletions in the dystrophin gene in Serbian cohort with dystrophinopathies" in Vojnosanitetski pregled, 77, no. 4 (2020):387-394,
https://doi.org/10.2298/VSP180226089M . .