The First Case Report of 47,XXY/46,XX/46,XY Mosaic Klinefelter Syndrome Patient With Mixed Connective Tissue Disorder.

Klinefelter syndrome (KS) mosaicism 47,XXY/46,XX/46,XY is an extremely rare disorder. Mixed connective tissue disorder (MCTD) is a systemic rheumatological disease with overlapping characteristic features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM)/dermatomyositis (DM), and rheumatoid arthritis (RA). It contains a higher titer level of U1-RNP and anti-RNP antibodies. A 50-year-old man was referred to our clinic with gynecomastia, lower extremity rash, persistent fever, arthralgia, muscle weakness, dry eye and mouth, Raynaud's phenomenon abnormal, and hormone levels. He was a follow-up patient for MCTD. Chromosome analysis of the patient revealed an abnormal karyotype of mos47,XXY/46,XX/46,XY. Fluorescence in situ hybridization (FISH) analysis indicated ish(SRYx1),(DZYx1)(DZX1x2)/ish (SRYx0),(DYZ1x0)(DZX1x2)/ish(SRYx1), (DZYx1)(DZX1x1). Although the prevalence of autoimmune diseases in Klinefelter syndrome is unknown, it is thought that the estimated frequency is higher than men, close levels to that of women. This might be explained by several genes that regulate the function of the immune system located on the X chromosome and the gene dosage mechanism that is the escape of X-inactivation in early embryogenesis for KS development. To the best of our knowledge, this is the first case to report a 47,XXY/46,XX/46,XY Klinefelter syndrome patient with MCTD.

The effect of medicarpin on PTEN/AKT signal pathway in head and neck squamous cell carcinoma.

Background/Aim: We aimed to investigate the in vitro modulating effects of medicarpin on the PI3K/AKT signal pathway gene expressions in head and neck squamous cell carcinoma (HNSCC). Materials and Methods: The effect of medicarpin on PTEN and other associated genes in the PTEN/AKT signal pathway was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, real-time quantitative polymerase chain reaction, and Western blot analysis in the SCCL-MT1 (HNSCC) and control (HEK-293) cell lines. Results: The IC50 dose was 80 µM as a result of medicarpin treatment on HNSCC cells (P = 0.0006). It was found that PTEN and AKT gene expressions increased after the medicarpin administration while PDK1 gene expression was decreased in SCCL-MT1 cells (P = 0.0002, P = 0.0003, and P = 0.05, respectively). Protein expression results showed that medicarpin-treated cells significantly increased in pAKT (P = 0.024), pPTEN (P = 0.032), and decreased pPDK1 (P = 0.059) in SCCL-MT1. Conclusions: Our data show that medicarpin modulates HNSCC cells by increasing the PTEN and decreasing PDK1 expressions. PDK1 gene expression effects mTOR pathway which may increase AKT gene. Our study suggests that both medicarpin extracts combination with the HNSCC drug may be more effective in cancer treatment. Future prospective studies that integrate molecular and pharmacogenetic studies are crucial for revealing the mechanism and preventive medical efforts.

Radiation exposure in pregnancy: outcomes, perceptions and teratological counseling in Turkish women.

BACKGROUND: Fetal effects of radiation are associated with the gestational week of exposure, dose, and duration of exposure, but the perception of risk of radiation in expecting mothers is greater than the actual risk of physical effects. OBJECTIVES: Evaluate the overestimation of the teratogenic risk in women exposed to radiation and the role of teratological counseling in minimizing preconceptions. DESIGN: Analytical, cross-sectional. SETTING: Tertiary care center, genetic diseases diagnosis center. PATIENTS AND METHODS: Out of 10 784 people who applied for teratological consultation between 2009 and 2018, pregnant women meeting inclusion criteria and exposed to radiation were selected as the study group; pregnant women without radiation exposure were selected as the control group. Two subgroups of the study group based on the week and dose of exposure were also analyzed. MAIN OUTCOME MEASURES: Abortion rate, termination recommendation rates before and after teratological counseling. SAMPLE SIZE: 461 pregnant exposed to radiation; 213 pregnant women without radiation exposure. RESULTS: Preterm birth and termination rates differed significantly between cases and controls (P=.038, P=.019, respectively). Termination recommendation at the first examination was more frequent for both the week of exposure overall and dose subgroups comparing cases and controls (P<.001). In the comparison of subgroups by week of exposure, only the miscarriage rate was statistically significant (P=.007). After teratological counseling termination decision rates were significantly decreased (P<.001). CONCLUSION: Subjective perceptions about the risks of radiation may lead to the termination of an otherwise wanted pregnancy. Teratological counseling is crucial for the prevention of termination of pregnancy, clarifying misinformation, and minimizing anxiety. LIMITATIONS: With the exception of measurable values as calculated doses of radiation, the conclusions are mostly derived from medical records and subjective responses of pregnant women. The termination rates in our study probably do not reflect the whole population. CONFLICT OF INTEREST: None.

Rare Findings in Cleidocranial Dysplasia Caused by RUNX Mutation.

Background Cleidocranial dysplasia (CCD, #MIM119600) is an autosomal-dominant skeletal dysplasia characterized by delayed closure of the cranial sutures, aplasia, or hypoplasia of the clavicles and dental abnormalities. These findings were accompanied by mobile and drooping shoulders, frontal and parietal bossing, hypertelorism, brachycephaly, short stature, supernumerary, and late erupting teeth. Radiographic studies can reveal involvement of multiple bones including skull, chest, pelvis, and limbs. CCD can be diagnosed with clinical and radiological evaluation and validated by molecular studies. Heterozygous loss of function RUNX2 gene, which plays an important role in osteogenesis and differentiation of precursor cells, causes CCD phenotype. Methods In this article, we reported five cases from three unrelated families with CCD phenotype. All exons and exonic-intronic boundary regions of RUNX2 gene from five patients were analyzed by polymerase chain reaction amplification and direct Sanger-sequencing. Results Our patients had classical CCD phenotype and we detected three different previously described mutations including c.1171C > T, IVS4 + 4delAAGT and c.676G > A. However, nail dysplasia has never been associated with these mutations. Our patients had varying degrees of nail dysplasia. Two of three mutations are related with Runt DNA-binding domain of RUNX2 protein in Wnt signaling and c.1171C > T had effect on proline/serine/threonine-rich (PST) domain. Recently, Wnt signaling pathway was presented as a key regulator of digit and nail differentiation. Our data suggest that RUNX2 gene may have an essential role on embryogenesis of nails, probably by protecting their integrity.

Determination of cytokine profile and associated genes of the signaling pathway in HNSCC.

Head and neck squamose cell carcinoma (HNSCC) is an aggressive group of tumors that are generally heterogeneous. Despite treatment advances, disease-free survival has not significantly improved. Therefore, it is of great importance to understand the molecular etiology of HNSCC and genetic alterations in the signal pathways in order to develop new therapeutic approaches. In this study, firstly we used a cytokine array to analyze the secretomes of HNSCC patients and healthy controls. In the next step, the results from the cytokine sequence were validated by qRT-PCR and western blot, including genes in the associated signaling pathway. In array analysis, the levels of EGF, IGF-1, IGFBP-1, and PDGFBB were significantly higher in patients than in the controls. The results of qRT-PCR analyses showed that expression levels of PDGFRB gene were significantly up-regulated (p = 0.006) and PTEN (p > 0.001) were significantly down-regulated in tumors compared with normal tissues. When groups (early vs. advanced) were compared, higher expression of IGFBP-1 was observed in the larynx (p = 0.045) and larynx + oral cavity tumors (p = 0.010) in an advanced stage. In western blot analysis, pEGFR, pIGF-IR, pIR-ß, pPDGFRB, and pAKT levels were upregulated, and pPTEN was downregulated in tumors. Based on our observations, determining the interactions of EGFR, PDGFRB, IGF-1R and PTEN or the activation of each might represent a promising new and innovative treatment approach in HNSCC patients. It seems clear that, in most cancers, effective targeted therapy may be involved the blockade of each one or multiple targets.

Evaluation of IL1B rs1143634 and IL6 rs1800796 Polymorphisms with Autism Spectrum Disorder in the Turkish Children.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder caused by genetic, environmental and immunological factors. It is known that neural development processes are affected by immune functions. The aim of this study is to evaluate the relationship between cytokines IL6 and IL1B gene polymorphisms in ASD. METHODS: DNA isolations were performed in 95 children diagnosed with ASD and 84 unrelated healthy children, single-nucleotide changes in IL6 (rs1800796) and IL1B (rs1143634) genes were determined by using Real-Time PCR (Real-Time Polymerase Chain Reaction) method. RESULTS: IL6 rs1800796 polymorphism presented an elevated risk for the development of ASD with CG genotype and dominant model (CG+GG vs. CC), CG+GG carriers (OR = 1.867, p = 0.057; OR = 1.847, p = 0.055, respectively). CT genotype in IL1B rs1143634 polymorphism associated with 2.33 times elevated risk of autism and showed a significant association compared to wild-type CC genotype (p = 0.02). IL1B rs1143634 polymorphism presented a significantly elevated risk for the development of ASD with recessive model (CC+CT vs.TT), TT genotype (OR = 8.145, p = 0.02). CONCLUSION: This study concludes that rs1143634 is associated with the risk of ASD in Turkish children. Determining these polymorphisms in a larger sample group may contribute to understanding the etiology of ASD and developing new treatment protocols. ABBREVIATIONS: ASD: Autism spectrum disorder; DNA: Deoxyribonucleic acid; IL6: Interleukin 6; IL1B: Interleukin 1 beta; Real-time PCR: Real-time polymerase chain reaction; JAK-STAT: The Janus kinase/signal transducers and activators of transcription; MAPK: The mitogen-activated protein kinase; 5'UTR: The 5' untranslated region; IL1α: Interleukin 1 alpha; IL-1Ra: Interleukin 1 receptor antagonist; NF-κB: Nuclear factor-kappa B; DSM-V: The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; M-CHAT: Modified Checklist for Autism in Toddlers; EDTA: Ethylenediaminetetraacetic acid; gDNA: Genomic DNA; HWE: Hardy-Weinberg equilibrium; ANK2: Ankyrin 2; NL3: Neuroligin-3; XRCC4: X-ray repair cross complementing 4.

The effectiveness of prolotherapy on failed rotator cuff repair surgery.

OBJECTIVES: The aim of the present study was to investigate the effectiveness of prolotherapy injections in the treatment of failed rotator cuff repair surgery. PATIENTS AND METHODS: Between May 2014 and March 2016, a total of 15 patients (5 males, 10 females; mean age 49.4±10.7 years; range, 33 to 71 years) with failed rotator cuff repair surgery who had at least six months of complaints and were refractory to at least of three months of conservative methods were included. Ultrasound-guided prolotherapy injections were performed under aseptic conditions, and the patients were instructed to carry out a home-based exercise program. Clinical assessment of shoulder function was performed using a visual analog scale (VAS) for pain, Shoulder Pain and Disability Index (SPADI), Western Ontario Rotator Cuff (WORC) Index, patient satisfaction and shoulder range of motion. All patients were examined at baseline, at Week 3, 6, and 12 and at the final follow-up visit. RESULTS: The intra-group comparison showed that the patients achieved significant improvements at all time points, compared to baseline as measured by VAS, SPADI, WORC index, and shoulder range of motion (p<0.001). Twelve patients (80%) reported excellent or good outcomes. CONCLUSION: Our study results show that prolotherapy is effective in the treatment of patients with failed rotator cuff repair surgery with significant improvements in the shoulder functions and pain relief.

WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome.

Locus heterogeneity characterizes a variety of skeletal dysplasias often due to interacting or overlapping signaling pathways. Robinow syndrome is a skeletal disorder historically refractory to molecular diagnosis, potentially stemming from substantial genetic heterogeneity. All current known pathogenic variants reside in genes within the noncanonical Wnt signaling pathway including ROR2, WNT5A, and more recently, DVL1 and DVL3. However, ∼70% of autosomal-dominant Robinow syndrome cases remain molecularly unsolved. To investigate this missing heritability, we recruited 21 families with at least one family member clinically diagnosed with Robinow or Robinow-like phenotypes and performed genetic and genomic studies. In total, four families with variants in FZD2 were identified as well as three individuals from two families with biallelic variants in NXN that co-segregate with the phenotype. Importantly, both FZD2 and NXN are relevant protein partners in the WNT5A interactome, supporting their role in skeletal development. In addition to confirming that clustered -1 frameshifting variants in DVL1 and DVL3 are the main contributors to dominant Robinow syndrome, we also found likely pathogenic variants in candidate genes GPC4 and RAC3, both linked to the Wnt signaling pathway. These data support an initial hypothesis that Robinow syndrome results from perturbation of the Wnt/PCP pathway, suggest specific relevant domains of the proteins involved, and reveal key contributors in this signaling cascade during human embryonic development. Contrary to the view that non-allelic genetic heterogeneity hampers gene discovery, this study demonstrates the utility of rare disease genomic studies to parse gene function in human developmental pathways.

Neonatal fractures as a presenting feature of LMOD3-associated congenital myopathy.

Nemaline myopathy is a rare inherited disorder characterized by weakness, hypotonia, and depressed deep tendon reflexes. It is clinically and genetically heterogeneous, with the most severe phenotype presenting as perinatal akinesia, severe muscle weakness, feeding difficulties and respiratory failure, leading to early mortality. Pathogenic variants in 12 genes, encoding components of the sarcomere or factors related to myogenesis, have been reported in patients affected with the disorder. Here, we describe an early, lethal presentation of decreased fetal movements, hypotonia, muscle weakness, and neonatal respiratory failure requiring ventilator support in three siblings from a consanguineous family. All exhibited perinatal fractures, and thus, a skeletal dysplasia was considered as possibly contributing to the phenotype. However, whole exome sequencing revealed a homozygous, loss-of-function pathogenic variant in LMOD3, which has recently been associated with nemaline myopathy and, in a subset of patients, perinatal fractures. This case demonstrates the importance of considering congenital neuromuscular disorders in the differential diagnosis of perinatal fractures.

Determining and Managing Fetal Radiation Dose from Diagnostic Radiology Procedures in Turkey.

OBJECTIVE: We intended to calculate approximate fetal doses in pregnant women who underwent diagnostic radiology procedures and to evaluate the safety of their pregnancies. MATERIALS AND METHODS: We contacted hospitals in different cities in Turkey where requests for fetal dose calculation are usually sent. Fetal radiation exposure was calculated for 304 cases in 218 pregnant women with gestational ages ranging from 5 days to 19 weeks, 2 days. FetDose software (ver. 4.0) was used in fetal dose calculations for radiographic and computed tomography (CT) procedures. The body was divided into three zones according to distance from the fetus. The first zone consisted of the head area, the lower extremities below the knee, and the upper extremities; the second consisted of the cervicothoracic region and upper thighs; and the third consisted of the abdominopelvic area. Fetal doses from radiologic procedures between zones were compared using the Kruskal-Wallis test and a Bonferroni-corrected Mann-Whitney U-test. RESULTS: The average fetal doses from radiography and CT in the first zone were 0.05 ± 0.01 mGy and 0.81 ± 0.04 mGy, respectively; 0.21 ± 0.05 mGy and 1.77 ± 0.22 mGy, respectively, in the second zone; and 6.42 ± 0.82 mGy and 22.94 ± 1.28 mGy, respectively, in the third zone (p < 0.001). Our results showed that fetal radiation exposures in our group of pregnant women did not reach the level (50 mGy) that is known to increase risk for congenital anomalies. CONCLUSION: Fetal radiation exposure in the diagnostic radiology procedures in our study did not reach risk levels that might have indicated abortion.

Evaluation and comparison of the effect of hypothermia and ozone on ischemia-reperfusion injury of skeletal muscle in rats.

BACKGROUND: Tourniquet-induced ischemia-reperfusion, which affects local and distant organs, is very common in orthopedic surgery. Hypothermia is used in traumatic tissue during ischemic period commonly. Ozone (O3) has been recommended as a novel therapeutic agent in various medical conditions. The objective of the study was to evaluate and compare the effect of hypothermia (H) and O3 on ischemia-reperfusion injury of skeletal muscle in rats by measuring oxidative parameters and inducible nitric oxide synthase (iNOS) levels. MATERIALS AND METHODS: Eighteen rats (Wistar albino) were separated into five groups randomly (sham, IR, IR + H, IR + O3, IR + H + O3; n = 6). The lower right extremity of all rats was subjected to 2 h of ischemia and 22 h of reperfusion clamping the common iliac artery and using the rubber-band technique at the level of the lesser trochanter under general anesthesia. Two hours of hypothermia were applied during the first 2 h of reperfusion in two groups. O3 was applied in two groups. All rats were sacrificed after the IR period with high dose of anesthesia. The tibialis anterior muscle and blood were saved. Levels of superoxide dismutase, glutathione peroxidase, MDA, NOx, and interleukin-1ß were measured in the muscle. Creatinine kinase, lactate dehydrogenase, aspartate aminotransferase, urea, creatinine, and electrolytes were measured in serum. Immunohistochemical iNOS staining was performed on muscle samples. RESULTS: The levels of MDA, NOx, and interleukin-1ß in muscle were raised in the IR group compared with those in the sham group. The same parameters were lower in the groups of IR + H, IR + O3, and IR + H + O3 compared with those in the IR group. Superoxide dismutase and glutathione peroxidase activities in muscle were lower in the IR group compared with those in the sham group; however, same parameters were higher in the groups of IR + H, IR + O3, and IR + H + O3 compared with those in the IR group. Score and intensity of iNOS staining in skeletal muscle in the IR group was increased compared with that in the sham group and decreased in the groups of IR + H, IR + O3, and IR + H + O3 compared with that in the IR group. Levels of creatinine kinase, aspartate aminotransferase, and K in the three treatment groups decreased compared with those in the IR group. CONCLUSIONS: These findings showed that hypothermia, which has more affect, and O3 decreased the tourniquet-induced IR injury in the rat's muscle-skeletal system by reducing the levels of oxidative and nitrosative stress parameters and enhancing antioxidant enzymes. Hypothermia and O3 had no synergistic effect. Hypothermic reperfusion and O3 preconditioning might be beneficial in skeletal muscle IR injury-associated tourniquet.

Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes.

Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder that presents with extensive phenotypic variability, including facial dysmorphism, developmental delay/intellectual disability (DD/ID), abnormal extremities, and hirsutism. About 65% of patients harbor mutations in genes that encode subunits or regulators of the cohesin complex, including NIPBL, SMC1A, SMC3, RAD21, and HDAC8. Wiedemann-Steiner syndrome (WDSTS), which shares CdLS phenotypic features, is caused by mutations in lysine-specific methyltransferase 2A (KMT2A). Here, we performed whole-exome sequencing (WES) of 2 male siblings clinically diagnosed with WDSTS; this revealed a hemizygous, missense mutation in SMC1A that was predicted to be deleterious. Extensive clinical evaluation and WES of 32 Turkish patients clinically diagnosed with CdLS revealed the presence of a de novo heterozygous nonsense KMT2A mutation in 1 patient without characteristic WDSTS features. We also identified de novo heterozygous mutations in SMC3 or SMC1A that affected RNA splicing in 2 independent patients with combined CdLS and WDSTS features. Furthermore, in families from 2 separate world populations segregating an autosomal-recessive disorder with CdLS-like features, we identified homozygous mutations in TAF6, which encodes a core transcriptional regulatory pathway component. Together, our data, along with recent transcriptome studies, suggest that CdLS and related phenotypes may be "transcriptomopathies" rather than cohesinopathies.

The role of miRNAs in cancer: from pathogenesis to therapeutic implications.

Cancer is still one of the dominating causes of deaths worldwide, although there have been important enhancements for detection and diagnosis of cancer recently. miRNAs are shown to participate in carcinogenesis of several types of tumors and their aberrant expression of miRNAs has been detected in cell lines, xenografts and clinical samples. miRNAs are thought to target and modulate the expression of more than 60% of human genes, which makes the expressional regulation by miRNAs the most abundant post-transcriptional regulation mode. Here, we have reviewed the most current literature to shed a light on the functions of miRNAs on human carcinogenesis. Possible roles of miRNAs in oncogenesis through both genetic and epigenetic changes occurring during cancer initiation, progression, invasion or metastasis are summarized.

A novel frameshift mutation and infrequent clinical findings in two cases with Dyggve-Melchior-Clausen syndrome.

Dyggve-Melchior-Clausen syndrome (DMC) (MIM #223800) is a rare autosomal-recessive type of skeletal dysplasia accompanied by variable degrees of intellectual disability (ID). It is characterized by progressive spondyloepimetaphyseal dysplasia leading to disproportionate short stature, microcephaly, and coarse facies. The radiographic appearance of generalized platyspondyly with double-humped end plates and the lace-like appearance of iliac crests are pathognomonic in this syndrome. The disorder results from mutations in the dymeclin (DYM) mapped to the 18q12-12.1 chromosomal region. Here, we report two cases with DMC: one with disproportionate short stature, developmental delay, and severe ID with a novel frameshift mutation (c.1028_1056del29) leading to a premature stop codon, and the second patient with classical clinical and radiological features of DMC with mild ID and rectal prolapse, which is very rare. The clinical diagnosis was confirmed with molecular analysis of DYM with a known mutation at c.580C>T (p.R194X). The parents and sibling of the second patient were heterozygous carriers with mild skeletal changes and short stature.

A novel EFNB1 mutation in a patient with craniofrontonasal syndrome and right hallux duplication.

Craniofrontonasal syndrome (CFNS, MIM #304110) is a rare X-linked dominant developmental disorder that shows paradoxically greater severity in affected females than in affected males. Our female patient with frontonasal dysplasia, craniosynostosis and additional malformations was consistent with CFNS. EFNB1, which encodes a member of the ephrin family of transmembrane ligands for Eph receptor tyrosine kinases, is the only gene in which mutation is known to cause CFNS. Here, we describe 402T>C, a novel de novo mutation on EFNB1. This mutation results in substitution of highly conserved isoleucine at 134th residue to threonine.

Recessive truncating NALCN mutation in infantile neuroaxonal dystrophy with facial dysmorphism.

BACKGROUND: Infantile neuroaxonal dystrophy (INAD) is a recessive disease that results in total neurological degeneration and death in childhood. PLA2G6 mutation is the underlying genetic defect, but rare genetic heterogeneity has been demonstrated. One of the five families we studied did not link to PLA2G6 locus, and in the family one of the two affected siblings additionally had atypical features including facial dysmorphism, pectus carinatum, scoliosis, pes varus, zygodactyly and bilateral cryptorchidism as well as cerebellar atrophy, as previously reported. METHODS: Sural biopsy was investigated by electron microscopy. PLA2G6 was screened for mutations by Sanger sequencing. In the mutation-free family, candidate disease loci were found via linkage analysis using data from single nucleotide polymorphism genome scans. Exome sequencing was applied to find the variants at the loci. RESULTS: PLA2G6 mutations were identified in four families including the one with an unusually severe phenotype that led to death within the first 2 years of life. In the remaining family, seven candidate loci totalling 15.2 Mb were found and a homozygous truncating mutation p.Q642X was identified in NALCN at 13q32.3. The patients are around 20-years-old. CONCLUSIONS: NALCN is the gene responsible for INAD with facial dysmorphism. The patients have lived to adulthood despite severe growth and neuromotor retardation. NALCN forms a voltage-independent ion channel with a role in the regulation of neuronal excitability. Our findings broaden the spectrum of genes associated with neuroaxonal dystrophy. Testing infants with idiopathic severe growth retardation and neurodegeneration for NALCN mutations could benefit families.

The effects of vigabatrin on rat liver antioxidant status.

The anti-epileptic drug vigabatrin was developed as an inhibitor of gamma-aminobutyric acid transaminase, and its ability to increase inhibition in the central nervous system led to its testing in an animal model. In animal models chronic use of vigabatrin is associated with irreversible myelin vacuolation. Antioxidant drugs change the antioxidant capacity of the body. Oxidative stress of the body increased when valproic acid and carbamazepine were used chronically. To assess whether vigabatrin may affect protein oxidation and lipid peroxidation, glutathione, glutathione peroxidase (GPx), and glutathione-S-transferase (GST) levels were studied in the livers of 57 rat fetuses after administration of vigabatrin to the mothers (19 in the first week of pregnancy, 20 in the second week, and 18 in the third week) and in 19 control rat fetuses without vigabatrin. We compared the results of administration of vigabatrin in each group with the controls. Rat fetus protein oxidation in group I (0.686 nmol/mg protein) and group II (0.723 nmol/mg protein) was higher than in the control group (0.388 nmol/mg protein). Lipid peroxidation (0.209, 0.224, 0.253 nmol/mg protein, respectively) and GPx levels (345.4, 329.0, 283.2 nmol/mg protein, respectively) of groups I, II, and III were higher than in the control group (0.104, 167.2 nmol/mg protein, respectively). GST in group II (79.2 nmol/mg protein) and group III (77.8 nmol/mg protein) were not different from that in the control group (78 nmol/mg protein). It was found that vigabatrin affected all the parameters that were studied, especially in group I, which was given the drug in the first week of pregnancy.

Neuroblastoma in a dysmorphic girl with a partial duplication of 2p caused by an unbalanced translocation.

A 1-year-old female child with multiple dysmorphic features including microcephaly, hypertelorism, a short philtrum, low set ears, a narrow high arched palate, micrognathia and growth retardation was found to have a de novo chromosome abnormality including a partial duplication of the short arm of chromosome 2 and a partial deletion of the long arm of chromosome 17. The clinical features of the case shared many similarities to previous reports of trisomy 2p. Three years later, ecchymotic spots appeared around the left ocular region. Further clinical and pathological examination confirmed the diagnosis of a neuroblastoma. This is the first case of an unbalanced translocation, 46, XX, der (17), t (2; 17) (p23; q25), showing the development of a neuroblastoma in addition to the dysmorphic features. We suggest that trisomy 2p including the N-myc proto-oncogene may have predisposed the patient to the development of a neuroblastoma.