22.5 MB DELETION OF 13q31.1-q34 ASSOCIATED WITH HPE, DWM, AND HSCR: A CASE REPORT AND REDEFINING THE SMALLEST DELETED REGIONS.

Partial deletion of the long arm of the chromosome 13, 13q deletion syndrome is a rare chromosomal disorder characterized by severe growth and mental retardation, microcephaly, facial dysmorphism, brain malformations (holoprosencephaly, Dandy-Walker malformation), distal limb defects, eye anomalies, genitourinary and gastrointestinal tract malformations (Hirschsprung's disease). Approximately 1.2 Mb region in 13q32 was suggested as minimal critical region which is responsible for severe mental and growth retardation and brain anomalies. Here we described a male patient with de novo interstitial deletion of 13q31.1-q34 associated with short stature, microcephaly, facial dysmorphism, clinodactyly, cryptorchidism, micropenis, epilepsy, HPE, DWM, and HSCR. According to the literature review, present case indicated that smallest deleted region associated with DWM and HPE might be located at the 13q32.3, limb defects 13q34, anogenital malformations 13q33.3-34, and HSCR 13q31.1-32.1.

A NEW ISOLATED 20q INTERSTITIAL DUPLICATION CASE AND ITS CLINICAL COMPARISON WITH SIMILAR ISOLATED CASES.

Duplications of 20q are rare. Here we report a 15 years old boy with de novo duplication of 17.1 Mb at chromosome 20q. We made a comparison with the other isolated 20q duplication cases. There are phenotypic similarities between the patients who have the same affected chromosomal regions. We also showed a clinical follow up of the patient. There may be a relationship with Glaucoma and Graves disease between the chromosomal region and these diseases may occur at the other patients when they get older.

Partial monosomy 8q and partial trisomy 9q due to the maternal translocation t(8;9(q24.3;q34.1): a case report.

Partial trisomy 9q34-qter and partial monosomy 8q24.3-qter are very rare chromosomal abnormalities. Characteristic features of partial trisomy 9q34-qter are hypotonia, developmental delay, mild intellectual disability, dolichocephaly, distinct facial phenotype, long and thin fingers, and cardiac anomalies. Unlike the partial trisomy 9q34-qter, partial monosomy 8q24.3-qter has no distinct phenotype. Here we report a four years old female patient with partial trisomy 9q34-qter and partial monosomy 8q24.3-qter due to the maternal translocation t(8;9)(q24.3;q34. I). She has developmental delay, brachycephaly, facial dysmorphism, hand and foot anomalies, bilateral hearing loss, cardiac defect and abnormal brain MRI findings. To the best of our knowledge, this is the first report of the combination of partial trisomy 9q and partial monosomy 8q.

A 45 X male patient with 7q distal deletion and rearrangement with SRY gene translocation: a case report.

Here we present a male newborn with multiple congenital anomalies who also has an extremely rare form of testicular disorder of sex development (DSD). His karyotype was 45X, without any mosaicism. SRY gene was positive by polymerase chain reaction (PCR), and rearranged on distal part of the 7th chromosome by fluorescence in situ hybridization (FISH) analysis. SRY, normally located on the Y chromosome, is the most important gene that plays a role in the development of male sex. SRY gen may be translocated onto another chromosome, mostly X chromosome in the XX testicular DSD. On the other hand very few cases of 45 X testicular DSD were published to date. Other clinical manifestations of our patient were compatible with distal 7 q deletion syndrome. To the best of our knowledge this is the first case of 45 X testicular DSD with SRY gene rearranged on the 7th autosomal chromosome.

Picomolar-Level Sensing of Cannabidiol by Metal Nanoparticles Functionalized with Chemically Induced Dimerization Binders.

Simple and fast detection of small molecules is critical for health and environmental monitoring. Methods for chemical detection often use mass spectrometers or enzymes; the former relies on expensive equipment, and the latter is limited to those that can act as enzyme substrates. Affinity reagents like antibodies can target a variety of small-molecule analytes, but the detection requires the successful design of chemically conjugated targets or analogs for competitive binding assays. Here, we developed a generalizable method for the highly sensitive and specific in-solution detection of small molecules, using cannabidiol (CBD) as an example. Our sensing platform uses gold nanoparticles (AuNPs) functionalized with a pair of chemically induced dimerization (CID) nanobody binders (nanobinders), where CID triggers AuNP aggregation and sedimentation in the presence of CBD. Despite moderate binding affinities of the two nanobinders to CBD (equilibrium dissociation constants KD of ∼6 and ∼56 µM), a scheme consisting of CBD-AuNP preanalytical incubation, centrifugation, and electronic detection (ICED) was devised to demonstrate a high sensitivity (limit of detection of ∼100 picomolar) in urine and saliva, a relatively short sensing time (∼2 h), a large dynamic range (5 logs), and a sufficiently high specificity to differentiate CBD from its analog, tetrahydrocannabinol. The high sensing performance was achieved with the multivalency of AuNP sensing, the ICED scheme that increases analyte concentrations in a small assay volume, and a portable electronic detector. This sensing system is readily applicable for wide molecular diagnostic applications.

A case of onycotricodysplasia with intellectual disability, without neutropenia.

Onychotrichodysplasia, a rare autosomal recessive disorder, presents with hypoplastic fingernails, trichorrhexis, chronic neutropenia, and psychomotor retardation. Here, we describe a rare presentation of a child with onycotrichodysplasia associated with intellectual disability, but without neutropenia. He had sparse, short, dry, curly hair, dysplastic nails and intellectual disability. In contrast to cases described earlier, our patient had normal neutrophil count.

Automotive suspension component behaviors driven on flat and rough road surfaces.

The objective of this study is to identify the behavior of the car suspension components subjected to road surface contours. Strain signals were measured by installing a strain gauge at the critical area of the coil spring and lower arm. The car was driven on a flat and rough road surface with speeds of 30-40 km/h and 10-20 km/h, respectively. According to the fatigue life assessments based on the strain-life approach, it was found that when the car was driven on the rough road, the components received higher stresses, contributing to a shorter fatigue life. The fatigue life of the coil spring when being driven on the rough road was 1,248 cycles to failure, which was more than 14 times shorter when being driven on the flat road, with 19,060 cycles to failure. Meanwhile the fatigue life of the lower arm being driven on the rough surface was 3,580 cycles to failure, which was almost 3,328 times shorter when being driven on the flat road, with 11,914,000 cycles to failure. The useful life of the coil spring was more than 625 times lower than the lower arm when driven on the flat road, whereas when driven on the rough road, the useful life of the coil spring was almost 3 times lower than the lower arm. In conclusion, the coil spring will fail more than 2 times faster than the lower arm. This is because the contour of the road surfaces provide a vertical load, directly working the coil spring which reduces the load vertically, while the lower arm functions to hold the load when turning.

A case of lower mesodermal defects sequence.

Here, we describe a stillborn fetus who had lower mesodermal defects sequence associated with craniorachischisis, anencephaly, bilateral pulmonary hypoplasia.

Determination of acute and chronic effects of cadmium on the cardiovascular system of rats.

In this study, the systemic hemodynamics induced by acute and chronic cadmium (Cd+2) intoxication in the cardiovascular system of rats using thoracic electrical bioimpedance were examined and the acute and chronic effects of Cd+2 intoxication on the activities of antioxidant enzymes and malondialdehyde (MDA) were compared. Also, in this study, ultrastructural changes in the heart and aorta of rats were evaluated. Thirty-eight male Wistar albino rats were randomly divided into control, acute, and chronic groups. Chronic group was administered by oral gavage an aqueous solution of CdCl2 for 60 days, at dose of 15 mg Cd+2/kg/day. Acute group was administered by oral gavage an aqueous solution of CdCl2 with a single dose of 15 mg Cd+2/kg. Cadmium increased the stroke volume and cardiac output of rats in the chronic group, but did not change the heart rate significantly. Antioxidant enzymes activities and MDA level significantly increased in the chronic group. In ultrastructural examination, there were widespread degenerative changes in heart muscle cells of the chronic group but endothelial cells and smooth muscle cells in the aorta tissue samples had normal morphological features in all groups. All of the findings indicate that Cd+2 toxication can cause deformation in heart muscle cells due to an increase in free radicals and lipid peroxidation. Also, this study has confirmed that a long-term-Cd+2 exposure increased stroke volume (SV) and cardiac output (CO), but did not change the heart rate (HR).

Fibroblast growth stimulation by extracts and compounds of Onosma argentatum roots.

The roots of Onosma argentatum are used traditionally in Turkey for wound healing and burns. The n-hexane-dichloromethane extract of the roots, and four shikonin derivatives (deoxyshikonin, acetyl shikonin, 3-hydroxy-isovaleryl shikonin and 5,8-O-dimethyl acetyl shikonin) isolated from the n-hexane-dichloromethane extract were investigated for their ability to stimulate the growth of human amnion fibroblasts. A range of concentrations was studied and the extract found to stimulate the growth of human amnion fibroblasts in vitro at 0.1 microg/mL whilst 5,8-O-dimethyl acetyl shikonin had the same effect at 0.05-5 microg/mL, although cytotoxicity was observed at 50 microg/mL for all samples. The extract and all the other isolated compounds showed cytotoxicity at 10 microg/mL with the extract and 3-hydroxy-isovaleryl shikonin showing cytotoxicity at 5 microg/mL. It is suggested that any wound healing effect of the roots of Onosma argentatum might be partly due to an additive effect of the shikonin derivatives present.

Effects of norepinephrine on NMDA-induced neurotoxicity in cerebellar granular cell culture of rat pups.

In this study, norepinephrine was tested in 0.1, 1, 10, 25 and 50 microM doses in 100 microM NMDA toxicity on cerebellar granular cell culture of rats. NMDA in 100 microM concentration induced cell death significantly with respect to controls. Death cell population was 1.08 +/- 0.44% in control and 22.15 +/- 2.46% in 100 microM NMDA (P < 0.0001). None of the norepinephrine concentrations administrated 15 min prior to NMDA was able to reduce death cell scores to control levels. Results were 8.75 +/- 0.83% in 0.1 microM, 7.0 +/- 1.01% in 1 microM, 17.25 +/- 1.31% in 10 microM, 35.5 +/- 1.38% in 25 microM and 17.9 +/- 1.72% in 50 microM norepinephrine plus 100 microM NMDA administrated groups (P < 0.0001 for all with respect to control). Labetalol, as an alpha and beta blocker in 0.5 microM concentration which was given 15 min prior to norepinephrine was able to block the effects of it. In comparison with 100 microM NMDA administered group, only low doses of norepinephrine reduced the death cell scores significantly (for 0.1 and 1 microM norepinephrine plus NMDA groups; P < 0.0001). For 10 and 50 microM norepinephrine plus NMDA groups, death cell scores were found statistically insignificant from the NMDA-administered group (P > 0.05 for both) while for the 25 microM norepinephrine plus NMDA group, the death cell score was found to be statistically increased (P < 0.0001).

High frequency of sister chromatid exchanges in lymphocytes of the patients with Behçet's disease.

Behçet's disease (BD) (OMIM 109650) is an immunogenetically based multisystem disease, characterized by iridocyclitis, arthritis, orogenital ulcerations and pustular skin lesions. Viral and autoimmune etiologies have been suggested and HLA-B5 has been found to predominate in BD. The disease is most seen in Turkey and Japan. Although familial cases have been reported, the mode of inheritance is not clear. To determine the genetic instability in BD, sister chromatid exchange (SCE) analysis has been performed on peripheral lymphocytes in 23 patients and 20 healthy controls. We found significantly higher SCE rates in the patient group (p < 0.0001). Our results may indicate that genetic impairment and genetic instability may play an important part in the etiology of BD.

Sister chromatid exchange analysis in patients exposed to low dose of iodine-131 for thyroid scintigraphy.

To determine the genotoxic risk associated with diagnostic exposure to low doses of iodine 131 (131I), sister chromatid exchange (SCE) analysis was performed in lymphocytes of 18 non-smoking women who received 370 kBq (10 microCi) intravenous 131I sodium iodide as an adjuvant for scintigraphy for diagnosing thyroid nodularity. SCE frequencies were measured before and after 131I administration. SCE results in the pre-treated phase were regarded as control. Although SCE values 24 h after 131I administration did not show a significant increment (p > 0.05), there was a significant increase 72 h after treatment (p < 0.05). These results indicate that genetic damage might be induced by low dose of 131I.

A Turkish case of subcortical/subependymal heterotopia associated with corpus callosum dysgenesis, craniofacial dysmorphism, severe eye abnormalities, and growth-mental retardation.

The patient is a 12-year-old boy with a history of learning disability, growth retardation, and strabismus. Weight, height and head circumference were below the 3rd percentile. A café-au-lait spot, 1x1 cm a diameter, on the back region and pectus excavatum deformity were diagnosed. He had facial asymmetry, a broad nose, sparse eyebrows and eyelashes, a rudimentary frontal sinus, deviation of the nasal septum, and bilateral small maxillary bones. The left orbital fossa was also mildly rudimentary. On eye examination the movements of the left globe to the upward and lateral side were limited and internal strabismus was noted at this side. Visual acuity was 1/10, bilaterally. Bilateral choroid coloboma, glaucoma, vertical and horizontal nystagmus were diagnosed. Fundoscopic examination revealed bilateral optic atrophy and macular and paramacular granulation tissues on the left side. Intelligence quotient was 46. Electroencephalography revealed bilateral frontal slow-wave activity. Visual evoked potential revealed prolonged p100 wave latencies bilaterally. Magnetic resonance imaging of the brain demonstrated corpus callosum dysgenesis, bilateral subcortical heterotopia in the frontal lobes and subependymal heterotopia in the posterior horn of the left ventricle. Chromosomal analysis revealed a normal male karyotype, 46, XY. Although several cases of heterotopia in association with mental retardation, craniofacial dysmorphism, cerebral, and eye abnormalities have been described the combination of abnormalities diagnosed in our case has not previously been reported. We hypothesize that the combination of subcortical/subependymal heterotopia, corpus callosum dysgenesis, craniofacial dysmorphism, severe eye abnormalities, and growth-mental retardation may be a new syndrome.

A review of 35 cases of asymmetric crying facies.

A review of 35 cases of asymmetric crying facies: Congenital asymmetric crying facies (ACF) is caused by congenital hypoplasia or agenesis of the depressor anguli oris muscle (DAOM) on one side of the mouth. It is well known that this anomaly is frequently associated with cardiovascular, head and neck, musculoskeletal, respiratory, gastrointestinal, central nervous system, and genitourinary anomalies. In this article we report 35 ACF patients (28 children and 7 adults) and found additional abnormalities in 16 of them (i.e. 45%). The abnormalities were cerebral and cerebellar atrophy, mega-cisterna magna, mental motor retardation, convulsions, corpus callosum dysgenesis, cranial bone defect, dermoid cyst, spina bifida occulta, hypertelorism, micrognatia, retrognatia, hemangioma on the lower lip, short frenulum, cleft palate, low-set ears, preauricular tag, mild facial hypoplasia, sternal cleft, congenital heart defect, renal hypoplasia, vesicoureteral reflux, hypertrophic osteoarthropathy, congenital joint contractures, congenital hip dislocation, polydactyly, and umbilical and inguinal hernia. Besides these, one infant was born to a diabetic mother, and had atrial septal defect and the four other children had 4p deletion, Klinefelter syndrome, isolated CD4 deficiency and Treacher-Collins like facial appearance, respectively Although many of these abnormalities were reported in association with ACF, cerebellar atrophy, sternal cleft, cranial bone defect, infant of diabetic mother, 4p deletion, Klinefelter syndrome, isolated CD4 deficiency and Treacher-Collins like facial appearance were not previously published.