ZORICA-ILEANA HERTZOG(1), D. HERTZOG(2)
(1)UMF Craiova, Facultatea de Medicină Dentară, disciplina de Genetică, (2)UMF Craiova, Facultatea de Medicină Dentară, disciplina de Farmacologie
REZUMAT
Introducere. In ultimii ani au fost inregistrate progrese remarcabile in identificarea determinantilor moleculari care controleaza dezvoltarea segmentului cefalic, in special dezvoltarea ochilor si a dintilor. Pentru ca toate aceste defecte oculare afecteaza calitatea vietii si, uneori, chiar viata, este necesar sa se identifice cauza genetica a acestor anomalii pentru formularea unui consult genetic corect si a unei strategii terapeutice adecvate. Lucrarea noastra işi propune sa realizeze un studiu genetic in cateva cazuri cu anomalii oculare asociate cu defecte dentare si sa formuleze o retea de semnalizare in care calea de semnalizare a dezvoltarii ochilor se intersecteaza cu aceea a dezvoltarii dintilor
Material si metode de lucru. Au fost luate in studiu 3 cazuri care au prezentat anomalii oculare. Pentru fiecare caz a fost efectuata analiza citogenetica, arborele genealogic si sa urmărit frecvenţa SCE (sister chromatid exchanges) induse cu bleomicină.
Rezultate. Intr-un caz diagnosticat cu sindrom Hallermann Streiff François, la care microftalmia a fost asociată cu incisivi de formă conică, analiza citogenetică a relevat un cariotip normal (46,XX). Intr-un alt caz, care a etalat microftalmie, strabism, blefaroptoză si anomalii dentare (hipodontie, implantare vicioasa), examenul citogenetic a evidentiat o delXq (16%) alaturi de un cariotip normal (84%). La al treilea caz, care a prezentat microftamnie si cataracta congenitala asociate cu dinti supranumerari (un mesiodens conic) si o usoara retardare mentala, am identificat un izodicentric X in 25% din metafazele examinate. Tratamentul culturilor de celule cu bleomicină, un cunoscut clastogen, a condus la o crestere semnificativa a SCE in toate cele trei cazuri in comparatie cu probele de control, obtinute de la donori voluntari. Analiza genealogica arata o transmitere autozomal recesiva in primele doua cazuri si o transmitere dominanta X-linkata in al treilea caz.
Concluzii. Frecventa crescuta a aberaţiilor cromozomiale şi a SCE induse demonstreaza o deficienta a enzimelor de reparare a leziunilor ADN. Este foarte posibil ca repararea defectuoasă a AND să contribuie la defectele oculare şi dentare. Asocierea microftalmiei cu anomalii dentare presupune existenta unei complexe retele de semnalizare in dezvoltarea segmentului cefalic in care diferiti factori de transcriptie (Pax6, Pax9, MITF) interactioneaza, iar mutatiile unei gene influenteaza negativ activitatea celorlalte gene.
CUVINTE CHEIE microftalmie, anomalii dentare, instabilitate cromozomială indusă, reţea complexă de semnalizare
Several genetic considerations regarding the association between microphtalmia and dental defects
ABSTRACT Introduction. Remarcable progresses in the identification of molecular determinants checking both the cephalic segment, and especially, eyes and teeth developments have been achieved in the last teeth developments have been achieved in the last teeth developments have been achieved in the last quality of life, and sometimes even the life itself, it is necessary that the genetical cause of these annomalies should be identifiedin order to formulate a correct genetic consulting and an adequate therapeutic strategy.
The aim of the paper has to achieve a genetic study in some cases with ocular anomalies associated to dental defects and also to formulate a signal pathway where that of the eyes development intersects to the dental development one. Material and methods. Three patients displaying ocular annomalies have been taken in study. Cytogenetic analysis, pedigree and SCE (sister chromatid exchanges) induced by bleomycin were performed for each case.
Results. In a case diagnosed with Hallermann – Streiff – François where microphtalmia has been associated with cone-shaped incisors, cytogenetic analysis shows a normal karyotype (46,XX). In the other case, which exhibited microphtalmia, blepharoptose and dental anomalies (hypodontia, mistaken teeth), the cytogenetic analysis emphasized del(Xq) (16%) and a normal karyotype (84%). In the third case with microphtalmia, congenital cataract, mesiodens cone-incisor and a slight mental retardation, we identified a isodicentric chromosome X in 25% examinated metaphases. The treatment of cell cultures with belomycin, a well-known clastogen, led to a significant increase of chromosomal aberrations and SCE in all the three cases with respect to control samples, obtined from health individuals. Genealogical analysis shows a recessive-autosomale transmission in the first 2 cases and dominante X-linkate in the third case.
Conclusions. The increased rate of induced chromosomal aberrations and SCE demonstrated a deficiency in repairing enzymes of DNA lesions. It is very possible that the defective repair of DNA to contribute to ocular and dental defects. The association between microphtalmia and dental deffects suggests the existence of an signaling inrtricate network in the development of the cephalic segment where different transcription factors (Pax6, Pax9, MITF) interact, and the mutations of a gene negatively influences the activity of the other genes
(1)UMF Craiova, Facultatea de Medicină Dentară, disciplina de Genetică, (2)UMF Craiova, Facultatea de Medicină Dentară, disciplina de Farmacologie
REZUMAT
Introducere. In ultimii ani au fost inregistrate progrese remarcabile in identificarea determinantilor moleculari care controleaza dezvoltarea segmentului cefalic, in special dezvoltarea ochilor si a dintilor. Pentru ca toate aceste defecte oculare afecteaza calitatea vietii si, uneori, chiar viata, este necesar sa se identifice cauza genetica a acestor anomalii pentru formularea unui consult genetic corect si a unei strategii terapeutice adecvate. Lucrarea noastra işi propune sa realizeze un studiu genetic in cateva cazuri cu anomalii oculare asociate cu defecte dentare si sa formuleze o retea de semnalizare in care calea de semnalizare a dezvoltarii ochilor se intersecteaza cu aceea a dezvoltarii dintilor
Material si metode de lucru. Au fost luate in studiu 3 cazuri care au prezentat anomalii oculare. Pentru fiecare caz a fost efectuata analiza citogenetica, arborele genealogic si sa urmărit frecvenţa SCE (sister chromatid exchanges) induse cu bleomicină.
Rezultate. Intr-un caz diagnosticat cu sindrom Hallermann Streiff François, la care microftalmia a fost asociată cu incisivi de formă conică, analiza citogenetică a relevat un cariotip normal (46,XX). Intr-un alt caz, care a etalat microftalmie, strabism, blefaroptoză si anomalii dentare (hipodontie, implantare vicioasa), examenul citogenetic a evidentiat o delXq (16%) alaturi de un cariotip normal (84%). La al treilea caz, care a prezentat microftamnie si cataracta congenitala asociate cu dinti supranumerari (un mesiodens conic) si o usoara retardare mentala, am identificat un izodicentric X in 25% din metafazele examinate. Tratamentul culturilor de celule cu bleomicină, un cunoscut clastogen, a condus la o crestere semnificativa a SCE in toate cele trei cazuri in comparatie cu probele de control, obtinute de la donori voluntari. Analiza genealogica arata o transmitere autozomal recesiva in primele doua cazuri si o transmitere dominanta X-linkata in al treilea caz.
Concluzii. Frecventa crescuta a aberaţiilor cromozomiale şi a SCE induse demonstreaza o deficienta a enzimelor de reparare a leziunilor ADN. Este foarte posibil ca repararea defectuoasă a AND să contribuie la defectele oculare şi dentare. Asocierea microftalmiei cu anomalii dentare presupune existenta unei complexe retele de semnalizare in dezvoltarea segmentului cefalic in care diferiti factori de transcriptie (Pax6, Pax9, MITF) interactioneaza, iar mutatiile unei gene influenteaza negativ activitatea celorlalte gene.
CUVINTE CHEIE microftalmie, anomalii dentare, instabilitate cromozomială indusă, reţea complexă de semnalizare
Several genetic considerations regarding the association between microphtalmia and dental defects
ABSTRACT Introduction. Remarcable progresses in the identification of molecular determinants checking both the cephalic segment, and especially, eyes and teeth developments have been achieved in the last teeth developments have been achieved in the last teeth developments have been achieved in the last quality of life, and sometimes even the life itself, it is necessary that the genetical cause of these annomalies should be identifiedin order to formulate a correct genetic consulting and an adequate therapeutic strategy.
The aim of the paper has to achieve a genetic study in some cases with ocular anomalies associated to dental defects and also to formulate a signal pathway where that of the eyes development intersects to the dental development one. Material and methods. Three patients displaying ocular annomalies have been taken in study. Cytogenetic analysis, pedigree and SCE (sister chromatid exchanges) induced by bleomycin were performed for each case.
Results. In a case diagnosed with Hallermann – Streiff – François where microphtalmia has been associated with cone-shaped incisors, cytogenetic analysis shows a normal karyotype (46,XX). In the other case, which exhibited microphtalmia, blepharoptose and dental anomalies (hypodontia, mistaken teeth), the cytogenetic analysis emphasized del(Xq) (16%) and a normal karyotype (84%). In the third case with microphtalmia, congenital cataract, mesiodens cone-incisor and a slight mental retardation, we identified a isodicentric chromosome X in 25% examinated metaphases. The treatment of cell cultures with belomycin, a well-known clastogen, led to a significant increase of chromosomal aberrations and SCE in all the three cases with respect to control samples, obtined from health individuals. Genealogical analysis shows a recessive-autosomale transmission in the first 2 cases and dominante X-linkate in the third case.
Conclusions. The increased rate of induced chromosomal aberrations and SCE demonstrated a deficiency in repairing enzymes of DNA lesions. It is very possible that the defective repair of DNA to contribute to ocular and dental defects. The association between microphtalmia and dental deffects suggests the existence of an signaling inrtricate network in the development of the cephalic segment where different transcription factors (Pax6, Pax9, MITF) interact, and the mutations of a gene negatively influences the activity of the other genes
KEY WORDS microphtalmia, dental anomalies, induced chromosomal instability, a signaling intricate network.