Revisiting Atrioventricular Septal Defects: Exploring Chromosomal Abnormalities, Cardiac and Extracardiac Anomalies in a Contemporary Prenatal Cohort.

To estimate if there is an association between partial AVSD with chromosomal abnormalities, cardiac and extracardiac malformations, and to report the outcomes of prenatally diagnosed AVSD in a large, contemporary cohort. This is a retrospective cohort study of 190 prenatally diagnosed fetal AVSD between 2014 and 2023. Type of AVSD (complete vs partial), additional cardiac findings, extracardiac findings, presence of a heterotaxy, results of prenatal karyotype, and pregnancy outcomes were documented and analyzed. A total of 190 cases of fetal AVSD were analyzed. Complete AVSDs comprised 141 (74.2%) of the cohort, while partial AVSDs comprised 49 (25.7%). Karyotype was completed in 131 cases, and in 98 (74.8%) cases chromosomal abnormalities were identified, with trisomy 21 being the most common (53/131, 40.5%). Complete AVSDs were associated with trisomy 21 (45.5%, p = 0.04), Isolated cases of complete AVSDs (p = 0.03). Partial AVSDs were associated with trisomy 18 (53.1%, p < 0.001). In cases of partial AVSDs with aneuploidies, 7 (70%) had an ostium primum defect and 20 (90.9%) of AV canal type VSD. Isolated partial AVSD had no clear association with aneuploidies. There were additional cardiac anomalies in 96 (50.5%) and extracardiac anomalies in 134 (70.5%) of the cohort. There were no differences between partial and complete AVSD in rate of additional cardiac and extracardiac anomalies. AVSD was part of a heterotaxy in 47 (24.7%) of cases, and heterotaxy was associated with complete AVSD in the majority of cases (43/47, 91.4%, p = 0.003). Fetal partial AVSDs are associated with trisomy 18. Fetal complete AVSDs, even isolated, are associated with trisomy 21. There were no differences in association of other aneuploidies, additional cardiac findings, or extracardiac anomalies between prenatally diagnosed complete AVSDs and partial AVSDs.

An analysis of factors affecting survival in prenatally diagnosed omphalocele.

OBJECTIVES: To estimate factors affecting survival in prenatally diagnosed omphalocele, factors predicting genetic abnormalities, and association of omphalocele and specific groups of anomalies. METHODS: A retrospective observational study was performed, analyzing data of all omphalocele cases diagnosed prenatally in the perinatology clinic of a referral center. Demographic data, characteristics of the omphalocele (size, content, associated anomalies), results of genetic testing, pregnancy outcomes and postnatal outcomes were analyzed. RESULTS: Sixty-nine fetuses with omphalocele were included. The prevalence of omphalocele in livebirth was 0.007 %. Overall survival during the study period was 73.9 %. Twenty-eight (71.7 %) out of 39 cases with associated anomalies who were born live, survived, whereas survival was 85.7 % in the isolated cases. The most common anomaly associated with omphalocele were cardiac defects with 42 %; followed by placental or umbilical cord anomalies (28.9 %), skeletal defects (27.5), genitourinary anomalies (20.2 %), central nervous system (18.8 %) and facial anomalies (7.2 %), respectively. Eighty-five percent of the fetuses had at least one additional anomaly or ultrasound finding. Skeletal abnormalities and staged surgical repair of omphalocele were associated with survival. Associated skeletal anomalies and staged repair significantly increase the risk of postnatal death (OR: 4.6 95 % CI (1.1-19.5) and (OR: 10.3 95 % CI (1.6-63.9), respectively). CONCLUSIONS: Associated skeletal abnormalities and staged surgical repair are negatively associated with postnatal survival.

Contribution of chromosomal microarray analysis and next-generation sequencing to genetic diagnosis in fetuses with normal karyotype.

AIM: The aim of this study was to investigate the contribution of chromosomal microarray analysis (CMA) and next-generation sequencing (NGS) to genetic diagnosis in fetuses with normal karyotype who underwent invasive testing for different indications. METHODS: The results of invasive genetic testing performed at a tertiary center between September 2020 and March 2022 were retrospectively analyzed. Indications for invasive tests were classified as fetal structural malformation, presence of soft markers, and high risk in screening tests. CMA results were classified as pathogenic or likely pathogenic (pCNVs), benign (bCNVs), and variants of unknown clinical significance (VOUS). RESULTS: A total of 830 invasive tests were performed and aneuploidy was detected in 11.2% of the fetuses. CMA was performed in 465 fetuses with normal karyotype, and pCNVs were detected in 6.9%. pCNVs were detected in 8.2% of fetuses with structural malformations, 6.5% in soft markers, and 4.7% in high risk in screening tests. Pathogenic variants were detected by NGS in 33.8% of fetuses with bCNVs. CONCLUSIONS: pCNVs can be significantly detected not only in fetuses with structural malformations, but also in invasive testing with other indications. NGS significantly contributes to genetic diagnosis in fetuses with structural malformations.

Can FMR1 CGG repeat lengths predict the outcome in ICSI cycles?

OBJECTIVES: The aim of this study was to assess relationship between CGG repeat lengths and ovarian reserve and response to controlled ovarian stimulation (COH). MATERIAL AND METHODS: This prospective cohort study was carried out on patients (n = 49) who were admitted to the in vitro fertilization (IVF) clinic of the Zeynep Kamil Women's and Children's Diseases Training and Research Hospital, University of Health Sciences. Women under 40 years of age with premature ovarian insufficiency underwent genetic analysis to determine CGG repeat lengths. Ovarian reserve was assessed for each participant and participants underwent ovarian hyperstimulation and intracytoplasmic sperm injection (ICSI) cycle. Relationships between ovarian reserve, cycle outcome and CGG repeat lengths were assessed. Variables including fertility assessment including ovarian reserve tests (Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Estradiol (E2), Prolactin (PRL), Thyroid stimulating hormone (TSH), Antimullerian hormone (AMH), antral follicle count (AFC) tests) and some IVF cycle characteristics were assessed in relation to number of CGG repeat numbers. RESULTS: None of the ovarian reserve tests and cycle characteristics was found to be correlated with CGG repeat lengths. Comparison of ovarian reserve tests and cycle characteristics revealed no difference between groups of women with CGG repeat length > 55 and CGG repeat length ≤ 55. Antimullerian hormone (AMH) was a significant predictor for cycle cancellation (AUC = 0.779, P = 0.008). AMH level > 0.035 was found to be the optimal cut off value to predict cycles reaching to embryo transfer with 71% sensitivity and 85% specificity. The rate of cycle cancellation was 71% in cases with AMH ≤ 0.035 whereas it was 20% in cases with AMH > 0.035 (p = 0.001). No difference was determined between groups with and without cycle cancellation in terms of CGG repeat lengths (55.3 vs. 53.9, p = 0.769). Among cycles reaching to embryo transfer stage, 3 (13.6%) pregnancies were achieved. CONCLUSIONS: Our data showed no relationship between CGG repeat lengths and ovarian reserve and response to controlled ovarian stimulation. This data also showed that no clinical difference between FMR gene mutation related POI and other etiologies.

Foetal thoracic hypoplasia: concomitant anomalies and neonatal outcomes.

The aim of the current study was to determine the frequency of concomitant anomalies in foetal thoracic hypoplasia and the neonatal outcomes of these pregnancies. This retrospective study included 49 cases of foetal thoracic hypoplasia. All of the cases had skeletal system anomalies. Head and face anomalies (36.7%) were the second most frequent accompanying foetal anomaly, and the least common anomaly was genital system anomalies (4.1%). During the follow-ups, 52.6% (n = 10) of the newborns died in the first 24 h of life, 10.5% (n = 2) in the neonatal period and 36.8% (n = 7) in the infantile period.IMPACT STATEMENTWhat is already known on this subject? Foetal thoracic hypoplasias are lethal anomalies due to inadequate pulmonary development. Data on the other system anomalies that accompany foetuses with thoracic hypoplasia are quite limited in the literature. Moreover, even if the lethal course of thoracic hypoplasia is known, the information on how long newborns will survive is unclear.What do the results of this study add? In this study, most of the cases have additional anomalies, especially skeletal system and head-face anomalies. Approximately half of the newborns with thoracic hypoplasia die within the first 24 h.What are the implications of these findings for clinical practice and/or further research? When we need to consult a family considering the outcome of thoracic hypoplasia, this study can be guiding and helpful. On the other hand, the effects of additional anomalies on the prognosis of foetal and neonatal period are not clear. More studies are needed to better understand the prognosis of thoracic hypoplasias.

Primary skeletal muscle lymphoma: A case report.

Primary lymphomas of the bone or skeletal muscle are rare. Three mechanisms of lymphomatous involvement of the muscle have been described, namely direct invasion from adjacent involved lymph nodes or bone, metastatic spread and, least commonly, primary muscle lymphoma. We herein present a rare case of primary mucle non-Hodgkin lymphoma with a description if the associated clinicopathological findings and a review of the relevant literature. A 41-year-old female patient was referred to our hospital with a painful mass in the right lower extremity. Following resection and histopathological examination, a diffuse large B-cell lymphoma originating from the muscle with cutaneous and subcutanenous infiltration was diagnosed. The patient received chemotherapy with six cycles of cyclophosphamide, hydroxydaunomycin, oncovin and prednisone (CHOP regimen) and a complete radiological response was achieved after six cycles of treatment.

A novel missense mutation, p.(R102W) in WNT7A causes Al-Awadi Raas-Rothschild syndrome in a fetus.

Al-Awadi-Raas-Rothschild syndrome (AARRS) is a rare autosomal recessive disorder which consists of severe malformations of the upper and lower limbs, abnormal genitalia and underdeveloped pelvis. Here, we present a fetus with severe limbs defects, including bilateral humeroradial synostosis, bilateral oligodactyly in hands, underdeveloped pelvis, short femora and tibiae, absence of fibulae, severely small feet, and absence of uterus. An autosomal recessively inherited novel mutation in WNT7A found in the fetus, c.304C > T, affects an evolutionarily well-conserved amino acid, causing the p.(R102W) missense change at protein level. The findings presented in this fetus are compatible with diagnosis of AARRS, expanding the mutational spectrum of limb malformations arising from defects in WNT7A.

Evaluation of maternal serum folate, vitamin B12, and homocysteine levels andfactor V Leiden, factor II g.20210G>A, and MTHFR variations in prenatallydiagnosed neural tube defects.

BACKGROUND/AIM: Neural tube defects (NTDs) are common congenital malformations that develop as a result of interactions between several genes and environmental factors. Many factors have been investigated in order to understand the etiology of NTDs, and many studies have identified folate intake as a common contributing factor. The exact etiology of the disease is still unknown. MATERIALS AND METHODS: In this study, we compared serum folate, vitamin B12, and homocysteine levels, along with common thrombophilia-related genetic variations, including factor V Leiden, factor II g.20210G>A, MTHFR c.677C>T, and MTHFR c.1298A>C, in 35 pregnant women with fetal NTDs and 38 pregnant women with healthy fetuses. RESULTS: A significant difference in serum vitamin B12 level and factor V Leiden frequency was detected between the two groups. On the other hand, serum folate, homocysteine levels, and factor II g.20210G>A, MTHFR c.677C>T, and MTHFR c.1298A>C were not significantly different in the NTD group compared to the controls. CONCLUSION: These results indicate that vitamin B12 supplementation along with folate may help in lowering NTD frequency. In addition, this is the first study that provides evidence for a possible relationship between increased NTD risk and factor V Leiden.

Evaluation of Factor V Leiden, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C gene polymorphisms in retinopathy of prematurity in a Turkish cohort.

BACKGROUND: To assess Factor V Leiden (FVL) (rs6025), Prothrombin G20210A (rs1799963), MTHFR C677T (rs1801133), and MTHFR A1298C (rs1801131) gene mutations as risk factors in the development of retinopathy of prematurity (ROP). MATERIALS AND METHODS: A total of 105 children were included in this cross-sectional study. Patients were divided into two groups. The study group consisted of 55 infants with a history of ROP and the control group comprised 50 healthy infants with term birth. All subjects were screened for the presence of certain mutations (FVL, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C) by Real-Time PCR at 1 year of age. RESULTS: The mean gestational age (GA) and birth weight (BW) of the study group were, 28.65 ± 2.85 weeks and 1171 ± 385.74 g, respectively. There were no significant differences of genotype and allele frequency of Prothrombin G20210A, MTHFR A1298C and MTHFR C677T between the study and control groups (p > 0.05). Eight children (14.5 %) had heterozygous and one child (1.8%) had homozygous FVL mutation in the study group. One child (2%) in the control group had heterozygous FVL mutation. There was statistically significant differences of FVL allele and genotype frequencies between the groups (p < 0.05). CONCLUSIONS: The prevalence of FVL polymorphism (16.3 %) was higher in ROP patients than control subjects in this Turkish cohort. We suggest a possible association of FVL mutation with ROP at the end of the study.

Molecular etiology of arthrogryposis in multiple families of mostly Turkish origin.

BACKGROUND: Arthrogryposis, defined as congenital joint contractures in 2 or more body areas, is a clinical sign rather than a specific disease diagnosis. To date, more than 400 different disorders have been described that present with arthrogryposis, and variants of more than 220 genes have been associated with these disorders; however, the underlying molecular etiology remains unknown in the considerable majority of these cases. METHODS: We performed whole exome sequencing (WES) of 52 patients with clinical presentation of arthrogryposis from 48 different families. RESULTS: Affected individuals from 17 families (35.4%) had variants in known arthrogryposis-associated genes, including homozygous variants of cholinergic γ nicotinic receptor (CHRNG, 6 subjects) and endothelin converting enzyme-like 1 (ECEL1, 4 subjects). Deleterious variants in candidate arthrogryposis-causing genes (fibrillin 3 [FBN3], myosin IXA [MYO9A], and pleckstrin and Sec7 domain containing 3 [PSD3]) were identified in 3 families (6.2%). Moreover, in 8 families with a homozygous mutation in an arthrogryposis-associated gene, we identified a second locus with either a homozygous or compound heterozygous variant in a candidate gene (myosin binding protein C, fast type [MYBPC2] and vacuolar protein sorting 8 [VPS8], 2 families, 4.2%) or in another disease-associated genes (6 families, 12.5%), indicating a potential mutational burden contributing to disease expression. CONCLUSION: In 58.3% of families, the arthrogryposis manifestation could be explained by a molecular diagnosis; however, the molecular etiology in subjects from 20 families remained unsolved by WES. Only 5 of these 20 unrelated subjects had a clinical presentation consistent with amyoplasia; a phenotype not thought to be of genetic origin. Our results indicate that increased use of genome-wide technologies will provide opportunities to better understand genetic models for diseases and molecular mechanisms of genetically heterogeneous disorders, such as arthrogryposis. FUNDING: This work was supported in part by US National Human Genome Research Institute (NHGRI)/National Heart, Lung, and Blood Institute (NHLBI) grant U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics, and US National Institute of Neurological Disorders and Stroke (NINDS) grant R01NS058529 to J.R. Lupski.

DNA damage is increased in lymphocytes of patients with metabolic syndrome.

We assessed DNA damage in patients with metabolic syndrome (MetS) by performing comet and micronucleus (MN) assays on peripheral blood lymphocyte cultures from study participants. 52 MetS patients and 35 age-matched healthy controls were evaluated for abdominal obesity, body-mass index (BMI), blood pressure, serum triglycerides, HbA1c, HDL-C, and fasting blood glucose levels. In addition, malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined. Serum levels of triglycerides, HbA1c, fasting blood glucose and waist circumference, systolic blood pressure, diastolic blood pressure, and BMI of the subjects in the MetS group were significantly higher than those of the control group (for each, p<0.001). However, the mean level of HDL-C in the MetS group was lower than in the control group (p<0.001). In the study, the length of comet tails was significantly higher in the MetS patients (10.23±1.98, range 5.72-15.08) than in the controls (3.12±1.73, range 0.6-7.1) (p<0.001). MN frequency was also significantly increased in MetS patients (3.68±1.27 per 1000 cells) compared to that of the control group (1.81±0.84 per 1000 cells) (p<0.001). Micronucleated cell frequency and comet-tail length in subjects showed positive correlations with waist circumference, BMI, and plasma triglyceride levels (p<0.01) and negative correlations with HDL-C levels (p<0.01). Among the oxidative stress factors, MDA levels were significantly higher in MetS patients than in the controls. However, SOD and GSH-Px enzyme activities were significantly lower in the MetS group than in the controls. These findings suggest that patients with MetS have increased DNA damage and oxidative stress.

Exome sequencing identifies a homozygous C5orf42 variant in a Turkish kindred with oral-facial-digital syndrome type VI.

Oral-facial-digital syndrome type VI (OFDVI) is a rare ciliopathy in the spectrum of Joubert syndrome (JS) and distinguished from other oral-facial-digital syndromes by metacarpal abnormalities with central polydactyly and by a molar tooth sign on cranial MRI. Additional characteristic features include short stature, micrognathia, posteriorly rotated low-set ears, hypertelorism, epicanthal folds, broad nasal tip, tongue hamartoma, upper lip notch, intraoral frenula, cleft lip/palate, and renal anomalies. Recently, novel mutations in C5orf42 were identified in 9 out of 11 OFDVI families. In a subsequent study C5orf42 was found to be mutated in only 2 out of 17 OFDVI probands while 28 patients with a pure JS phenotype also had pathogenic mutations of C5orf42. We report on two affected cousins diagnosed with OFDVI who were born from first degree cousin marriages. Whole exome sequencing (WES) identified a homozygous predicted damaging missense mutation (c.4034A > G; p.Gln1345Arg) in the C5orf42 gene. Our data contribute to the evidence that C5orf42 is one of the causative genes for OFDVI.

Whole-exome sequencing links TMCO1 defect syndrome with cerebro-facio-thoracic dysplasia.

Whole-exome sequencing (WES) is a type of disruptive technology that has tremendous influence on human and clinical genetics research. An efficient and cost-effective method, WES is now widely used as a diagnostic tool for identifying the molecular basis of genetic syndromes that are often challenging to diagnose. Here we report a patient with a clinical diagnosis of cerebro-facio-thoracic dysplasia (CFTD; MIM#213980) in whom we identified a homozygous splice-site mutation in the transmembrane and coiled-coil domains 1 (TMCO1) gene using WES. TMCO1 mutations cause craniofacial dysmorphism, skeletal anomalies characterized by multiple malformations of the vertebrae and ribs, and intellectual disability (MIM#614132). A retrospective review revealed that clinical manifestations of both syndromes are very similar and overlap remarkably. We propose that mutations of TMCO1 are not only responsible for craniofacial dysmorphism, skeletal anomalies and mental retardation syndrome but also for CFTD.

Phototherapy causes a transient DNA damage in jaundiced newborns.

In this study, we aimed to clarify the following questions: 1) Does phototherapy (PT) cause genotoxicity in full-term newborn babies undergoing PT as a result of neonatal jaundice?, 2) if genotoxic effect occurs, is there any relationship between the duration of PT and genotoxicity?, and 3) is genotoxic effect temporary or not? The frequency of sister chromatid exchange (SCE) was determined in jaundiced newborns before, during, and after phototherapy, then determined again in childhood (approximately 3.5 years old). Mean frequency of SCE of 22 full-term jaundiced babies significantly increased during the PT procedure and in every single day, compared to the previous day, in comparison to the pre-PT basal value (6.20 ± 0.57;); mean SCE frequencies at 24, 48, 72, and 96 hours were 7.75 ± 0.40, 8.16 ± 0.47, 8.50 ± 0.40, and 9.36 ± 0.55, respectively (all P-values <0.01). In childhood, no significant difference was found between the mean SCE value (4.9 ± 0.9) of 20 of 22 children, who received PT in the neonatal period, and the mean SCE value (4.7 ± 0.6) of 20 coevaluated healthy children (P = 0.40). This study demonstrates that the negative effect of PT on SCE is a temporary effect.

Genetic alterations in benign, preneoplastic and malignant breast lesions.

CONTEXT: The c-erbB-2 proto-oncogene is a member of the epidermal growth factor receptor family and has been associated with a more aggressive breast tumor biology and resistance to some types of treatments. AIMS: The aim is to investigate the correlation among bcl-2 and c-erbB-2 and the micronucleus (MN) formation in patients with early breast cancer (BC). MATERIALS AND METHODS: This study was conducted between May 2010 and December 2011. We analyzed the MN frequencies in 15 patients with invasive breast carcinoma (IBC), 13 patients with intraductal proliferative lesion (IDPL) and 12 benign breast lesion (BBL). The sample consisted of 40 formalin-fixed, paraffin-embedded blocks of benign and malignant breast tissue. The specimens were evaluated for bcl-2 or c-erbB-2 immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40Χ magnification and recorded as the percentage of c-erbB-2 and bcl-2 positive tumor cells over the total number of cells examined in the same area. The percentage scores were subsequently categorized using the 5% cut-off point for positive staining. RESULTS: The MN was significantly increased in IBC and in IDPL patients compared to BBL patients (3.82 ± 0.17 and 2.37 ± 0.52, respectively, vs. 1.61 ± 0.40, P < 0.001). On other hand, the MN frequencies in IBC patients were higher than those in IDPL patients (3.82 ± 0.17 vs. 2.37 ± 0.52, P < 0.01). c-erbB-2, had the highest record in IBC (60%), and the score was not observed in both IDPL and BBL: bcl-2 immunostaining was also assessed, the lowest recorded score was in IBC (46.66%) and the highest in both BBL and IDPL (100%). Furthermore, there was a significantly difference in the mean MN frequency between c-erbB-2 positive IBC patients (4.06 ± 0.48) and c-erbB-2 negative IBC patients (3.44 ± 0.39) (P < 0.05). CONCLUSIONS: Our results suggest that increased chromosome / DNA instabilities may be associated with the pathogenesis of early BC.

Apical root resorption caused by orthodontic forces: A brief review and a long-term observation.

External apical root resorption (ARR) is a common iatrogenic consequence of orthodontic treatment. One of the aims of this article is to present a brief overview of the literature, including; diagnosis and etiology, with emphasis on orthodontic forces to facilitate an understand of the prevention or management of ARR in orthodontic patients. We also present a long-term follow-up observation of severe ARR, including the last obtained cone beam computed tomography (CBCT) records, to demonstrate the effect of orthodontic forces on ARR.

Comet assay and analysis of micronucleus formation in patients with rheumatoid arthritis.

Oxidants play a significant role in causing oxidative stress, which underlies the pathogenesis of rheumatoid arthritis (RA). Genetic factors that predispose individuals to RA are considered to play an important role in the development of the disease. The aim of this study was to determine, by use of the comet assay and the micronucleus (MN) test, whether DNA damage has an effect on the pathogenesis of RA. Furthermore, our aim was to show if there is an association between oxidative stress and DNA damage in RA. This study was conducted between January and June 2010 in the Erzurum Training and Research Hospital. We analyzed lymphocytes from patients with RA (12 in active and 31 in inactive periods) and 30 healthy controls for effects in the comet assay and the MN test. In addition, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD), the activity of glutathione peroxidase (GSH-Px), the erythrocyte sedimentation rate (ESR) and the high-sensitivity C-reactive protein (hs-CRP) rate were determined in all the subjects. The comet-tail length, the MN frequencies and the MDA levels were significantly higher in patients--both in the active and the inactive period--than in the controls. In contrast, the SOD and GSH-Px levels were significantly lower in both patient groups than in the controls. Our results suggest that an increased plasma MDA level and decreased plasma GSH-Px and SOD levels reflect the higher degree of oxidative stress in RA patients, a situation that may impair genetic stability in those patients. Thus, the results suggest that increased DNA damage may play an important role in the pathogenesis of RA.

Genomic instability in patients with Barrett's esophagus.

Our study aimed to determine, by counting sister chromatid exchange (SCE) and micronucleus (MN) frequencies, whether genetic impairment and DNA damage have an effect on the pathogenesis of Barrett's esophagus (BE). This study was conducted between June 2007 and November 2008 in the Erzurum Training and Research Hospital. We analyzed SCE and MN frequencies in 30 patients with BE, and in 30 control cases. SCE was significantly increased in BE patients compared with controls (6.89 +/- 1.04 vs. 5.01+/- 0.88, P < 0.001). Similarly, MN was significantly increased in BE patients compared with controls (3.48 +/- 1.08 vs. 1.83 +/- 0.64, P < 0.001). Our data indicate that the increased SCE and MN rates in lymphocytes of patients with BE may reflect genomic instability or deficiency of DNA repair capacity.

Orthodontic treatment of an ankylosed maxillary central incisor through osteogenic distraction.

Tooth ankylosis is one of the various problems in dentistry and requires special treatment approaches for satisfactory results. In the orthodontic treatment of an ankylosed tooth, different treatment modalities have been put into practice including both orthodontic and orthodontic-surgical approaches. For favorable results, gingival margin esthetics must be considered as much as leveling the ankylosed tooth in the arch. Distraction osteogenesis accompanied by orthodontic mechanics is a sensible way of achieving this goal. However, devices used in the distraction protocol are high in price and bulky in shape, causing functional and esthetic problems for the patient. This report describes treatment of an infrapositioned ankylosed incisor with continuous distraction forces produced by conventional orthodontic mechanics. In conclusion, the ankylosed tooth was leveled in the upper arch successfully with a harmonic gingival margin.