Clinical findings in cases with 9q deletion encompassing the 9q21.11q21.32 region.

Tug E, Ergün MA, Perçin EF. Clinical findings in cases with 9q deletion encompassing the 9q21.11q21.32 region. Turk J Pediatr 2018; 60: 94-98. We report on a case with developmental delay and dysmorphic craniofacial features, and a novel~15.2 Mb interstitial deletion within 9q21.11q21.32 confirmed with array comparative genomic hybridization (aCGH). A twenty-two month old boy with inability to walk without support, absent speech, and attention deficit and hyperactivity disorder was seen in our clinic. His craniofacial examination revealed relative macrocephaly, facial asymmetry, frontal bossing, sparse medial eyebrows, hypertelorism, broad base to nose, smooth philtrum, large mouth, operated cleft lip and wide spaced teeth. The high resolution binding (HRB) chromosome analysis revealed an interstitial deletion 46,XY,del(9)(q21) confirmed by aCGH revealing; 46,XY,der(9)(pter→q21.11::q21.32→qter).arr9q21.11q21.32(71,069,763-86,333,272)X1dn. Genotype-phenotype correlations of sixteen cases with 9q21 deletion having different breakpoints and variable length revealed common characteristic features including severe developmental delay, epilepsy, neuro-behavioural disorders and facial dysmorphism including hypertelorism, smooth philtrum and thin upper lip. The smallest overlapping deleted region in all defined cases to date including our case comprised four genes. Among these deleted genes as in our case, especially RORB is considered to be a strong candidate for neurological phenotype.

Analysis of genetics and risk factors of Alzheimer's Disease.

Alzheimer's Disease is the leading neurodegenerative cause of dementia. The pathogenesis is not clearly understood yet, is believed to be the complex interaction between genetic and environmental factors. Consequently vascular risk factors and Apolipoprotein E genotyping are increasingly gaining importance. This study aimed at assessing the relationships between Alzheimer's Disease and Apolipoprotein E phenotype and vascular risk factors. Patients diagnosed with "possible Alzheimer's Disease" in the Gazi University, Department of Neurology, were included in the study and age-matched volunteer patients who attended the polyclinic were included as a control group. In this study, the risk factors including low education level, smoking, hyperlipidemia, higher serum total cholesterol levels, and hyperhomocysteinemia were found to be statistically significantly more common in the Alzheimer's Disease group in comparison to the Control Group, while all Apolipoprotein E ε4/ε4 genotypes were found in the Alzheimer's Disease group. The presence of the Apolipoprotein E ε4 allele is believed to increase vascular risk factors as well as to affect Alzheimer's Disease directly. The biological indicators which are used in identifying the patients' genes will be probably used in the treatment plan of the patients in the future.

SUBMICROSCOPIC DUPLICATION OF 8q24.3 REGION IS A POTENTIAL CANDIDATE FOR DISORDERS OF SEX DEVELOPMENT.

Some of the disorders of sex development (DSD), including 46, XX testicular DSD formerly called "XX maleness" and 46, XY DSD with partial or complete gonadal dysgenesis primarily affect the gonads. Genetic alterations in ten unrelated females with complete 46, XY gonadal dysgenesis (GD) were analyzed using an Array 2.7 M platform with whole genome coverage. The analysis result suggested that the most significant region maps to chromosome 8q24.3 which were previously reported by another independent study with a similar patient cohort and this region being probable candidate related to complete 46, XY GD.

MECP2 DUPLICATION SYNDROME WITH ADDITIONAL FINDINGS.

Rett syndrome (RTT) and Angelman syndrome (AS) are devastating neurological disorders that participate in overlapping clinical features with autism spectrum disorders (ASDs). It has been reported that in addition to common mutations or deletions, individuals with chromosomal duplications including either the MECP2 or UBE3A loci show clinical features related to those of MECP2 duplication syndrome, AS, or ASDs. Here we report a 10-year--10-months old male patient having overlapping clinical features of MECP2 duplication syndrome, AS and ASDs. He had mental retardation, lack of speech and developmental delay, and also dysmorphic features such as plagiocephaly, retrognathia, hyperextensible joints in fingers and elbows, broad great toe and three different sizes of cafe au laits. The X-ray revealed compound craniosynostosis and the cranial MRI at 10 years showed delayed myclination. Due to his clinical features, we performed molecular karyotyping and found numerous genomic alterations. Two of these genomic alterations including duplications of chromosome Xq28 and 15qll.2ql3.l1 were found to be compatible with his clinical findings. According to methylation analysis, duplicated UBE3A gene found to be not methylated. The present case study may contribute to a better definition and an improved comprehension of the overlapping pathways of MECP2 and UBE3A.

Protective effect of curcumin on priapism and ischemia-reperfusion injury in rats.

OBJECTIVE: We aimed to identify the oxidative stress effects of the ischemic priapism on cavernosal tissues and to assess the biochemical and histopathological effects of curcumin in rats. MATERIALS AND METHODS: 26 adult male Sprague Dawley rats were randomly divided into three groups. Group 1 (Control, n = 8): only penectomy was performed and 3 ml blood samples were obtained from the vena cava inferior (VCI). Group 2 (ischemia-reperfusion group; n= 8): penectomy was performed after 1 hour ischemic priapism + 30 min reperfusion and 3 ml blood samples were obtained from the VCI. Group III (IR + CURC group, n = 10): 200 mg/kg/day curcumin per orally before surgery for 7 days + penectomy after 1 hour ischemic priapism + 30 min reperfusion and 3 ml blood samples from the VCI. Total oxidant status (TAS), total antioxidant status (TAS) and paraoxonase (PON1) levels were measured. Tissue samples were investigated and scored histopathologically in terms of bleeding, edema and necrosis. RESULTS: TOS levels were higher (p = 0.002), and TAS levels were lower (p = 0.001) in the IR group compared to the control group. As a result of curcumin treatment, TAS levels were increased (p = 0.003), and TOS levels were decreased (p = 0.004) in the IR + CURC group compared to the IR group. In the treatment group (IR + CURC) TAS and TOS levels were similar to levels in the control group. PON1 levels were increased with ischemia-reperfusion (p = 0.21) and decreased with curcumin treatment (p = 0.53), however these changes were not statistically significant. There was no significant difference in the effects of curcumin on histopathological changes. CONCLUSIONS: This study showed that curcumin has preventive effects on oxidative stress parameters against ischemia-reperfusion injury.

A PATIENT WITH PARTIAL CHROMOSOME 12q DUPLICATION AND 10q DELETION.

Chromosomal deletions and/or duplications are relatively common cytogenetic abnormalities. Clinical findings depend on pure or complex forms of the anomaly, the location and size. In those cases, using current analytical technologies increases the possibility of discovering candidate genes that were not detected by conventional karyotyping responsible for these features. Here, we report an 18-month-old girl with prenatal and postnatal growth retardation, secundum ASD and PDA, facial dysmorphic features including frontal bossing, arched eyebrows, hypertelorism, wide nasal bridge and chronic diarrhea. Chromosome analysis on the peripheral leukocytes showed a 46,XX del(10)(q26.3),dup(12)(q24.11-q24.33) dn karyotype. An array-CGH analysis was performed to understand which genes were located on the deletion and duplication regions and what was their relationship with the phenotype. Based on our analyses, the deletion of the CALY gene on Chromosome 10q and the duplication of PTPN11 and TBX5 genes on chromosome 12q were possibly relevant for the clinical findings with our patient.

TEI Index in elite sprinters and endurance athletes.

AIM: Aerobic training has been reported to have a positive effect on myocardial performance index. The aim of the present study was to examine the myocardial performance index (MPI) in sprinters and endurance athletes. METHODS: A total of 66 elite male athletes (36 sprinter and 30 endurance athletes) and 33 agematched sedentary controls voluntarily participated in the study. The echocardiographic evaluation was performed and TEI index was measured as a marker of myocardial performance index in all groups. RESULTS: Demographic features, training ages and weekly exercise volumes were similar in sprinters and endurance athletes. There were no significant differences in terms of diastolic parameters and among the groups. In sprinters, isovolumetric relaxation time (IVRT) and isovolumetric contraction time (IVCT) were significantly shorter than in controls. In endurance athletes, IVCT was significantly shorter than in controls. Both sprinters and endurance athletes had longer ET compared with controls. TEI Index was significantly lower in sprinters and endurance athletes than in controls. CONCLUSION: Our results suggest that both aerobic and anaerobic training seem to have a positive effect on myocardial performance. This comparable effect might be a result of frequently exercising, especially aerobic exercising in sprinters' training programs.

Ketamine is toxic to chondrocyte cell cultures.

Ketamine has been used in combination with a variety of other agents for intra-articular analgesia, with promising results. However, although it has been shown to be toxic to various types of cell, there is no available information on the effects of ketamine on chondrocytes. We conducted a prospective randomised controlled study to evaluate the effects of ketamine on cultured chondrocytes isolated from rat articular cartilage. The cultured cells were treated with 0.125 mM, 0.250 mM, 0.5 mM, 1 mM and 2 mM of ketamine respectively for 6 h, 24 hours and 48 hours, and compared with controls. Changes of apoptosis were evaluated using fluorescence microscopy with a 490 nm excitation wavelength. Apoptosis and eventual necrosis were seen at each concentration. The percentage viability of the cells was inversely proportional to both the duration and dose of treatment (p = 0.002 and p = 0.009). Doses of 0.5 mM, 1 mM and 2mM were absolutely toxic. We concluded that in the absence of solid data to support the efficacy of intra-articular ketamine for the control of pain, and the toxic effects of ketamine on cultured chondrocytes shown by this study, intra-articular ketamine, either alone or in combination with other agents, should not be used to control pain. Cite this article: Bone Joint J 2014; 96-B:989-94.

Components of pain assessment after laparoscopic donor nephrectomy.

BACKGROUND: Pain after laparoscopic surgery can be divided into three components: incisional or superficial wound pain, deep intra-abdominal pain and referred shoulder pain. Better understanding and adequate assessment of post-operative pain may be an important clue to the optimisation of recovery after laparoscopic surgery. Therefore, we performed a components of pain assessment after laparoscopic donor nephrectomy. METHODS: Twenty patients who underwent a laparoscopic donor nephrectomy were included in this prospective study. Pain was subdivided into three components: superficial wound pain, deep intra-abdominal pain and referred shoulder pain, and for each component a numeric rating scale (from 0 to 10) was obtained at 1, 24 and 48 h after surgery. RESULTS: Repeated measurements analysis of variance showed that during the first 48 h after surgery, the superficial wound and deep intra-abdominal pain components were significantly higher as compared with the referred shoulder pain component. Although the deep intra-abdominal pain component was slightly higher as compared with superficial wound pain, this difference was not significant (P = 0.097). Further assessment of superficial wound pain showed that the Pfannenstiel incision was the most significant determinant of this component of pain (P = 0.004), whereas deep intra-abdominal pain was significantly higher at the ipsilateral side of the abdomen (P = 0.015). DISCUSSION: The components of pain assessment revealed that pain related to the Pfannenstiel incision and the deep intra-abdominal pain component are the most important determinants of pain after laparoscopic donor nephrectomy. Further improvement of the management of post-operative pain should focus on these components of pain.

The effects of constipation on the quality of life of children and mothers.

This study, a quasi-experimental study, was planned to investigate the effects of functional constipation on the quality of life (QOL) of children and their mothers. The sample of the study included children with functional constipation and its complications and their families (n=26). The Pediatric Quality of Life Inventory (PedsQL) and Short Form Health Survey-36 (SF-36) were used. No statistically significant difference was found by SF-36 QOL scale scores of the first and sixth month interviews with the mothers. There was a statistically significant difference in total psychosocial scores of the children. When the PedsQL scores, which were completed during the first and sixth month interviews with the mothers, were compared, there were no statistically significant differences between total physical health scores, total psychosocial scores and total inventory scores.

The evaluation of long-term effects of ionizing radiation through measurement of current sister chromatid exchange (SCE) rates in radiology technologists, compared with previous SCE values.

Ionizing radiation is a strong physical mutagen, causing breakage of phosphodiester bonds in DNA at any stage of the mitotic cycle. Analysis of sister chromatid exchange (SCE) has come into use as a sensitive DNA-damage indicator. We investigated the SCE rates in radiology technologists who are occupationally and chronically exposed to ionizing radiation. The study included 39 radiology technologists and 35 sex- and age-matched healthy controls. There was a statistically significant difference in the SCE frequency between radiology technologists and controls (p<0.0001). Additionally, previous SCE data of 10 radiology technologists were compared with current results regarding radiation exposure time. There was statistically significant difference between previous and current SCE values (p=0.005). The significant increase in the frequency of SCE in radiology technologists emphasizes the importance of radiation-protection procedures in order to minimize radiation exposure and avoid possible genotoxic effects. Comparison of two studies that measured SCE values of radiology technologists after 8 years also suggests that the genotoxic effect is reversible. In conclusion, radiation is still an important mutagenic agent despite improvements in daily working hours and conditions.

Effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in breast cancer patients.

The aim of this study was to explore the effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in patients who completed breast cancer treatment. Sixty breast cancer patients were randomised into three groups, as supervised exercise group, home exercise group and education group. Angiogenesis and apoptosis-related cytokine levels and quality of life (EORTC QOL-C30: European Organisation for Research and Treatment of Cancer Quality of Life C30), fatigue (Brief Fatigue Inventory) and depression (BDI: Beck Depression Inventory) scores were compared before and after a 12-week exercise programme. After the exercise programme, statistically significant decreases were found in interleukin-8 and neutrophil activating protein-78 levels in the home exercise group (P < 0.05). The education group showed a statistically significant increase in monocyte chemoattractant protein-1 level (P < 0.05). Functional score and global health score of EORTC QOL-C30 in the supervised exercise group and functional score of EORTC QOL-C30 in the home exercise group increased significantly after exercise programme (P < 0.05). BDI score was significantly lower in the supervised exercise group after the exercise programme (P < 0.05). Changes in angiogenesis and apoptosis-related molecules in the study groups suggest a possible effect of exercise on these parameters. Exercise programmes are safe and effective on quality of life and depression in breast cancer patients whose treatments are complete.

Molecular karyotyping of an isolated partial trisomy 11q patient with additional findings.

Isolated partial duplication of the long arm of chromosome 11 is very rare. The main features are dysmorphic facial features, pre/postnatal growth retardation, speech delay, mental retardation, hypotonia, microcephaly, and cardiac, vertebral, limb and genital anomalies. In this case, we report a patient with partial trisomy of 11q13.5→qter due to a de novo rearrangement consisting of the whole X chromosome and part of chromosome 11; 46,X,der(X)(Xqter→Xp22.33::11q13.5→11qter). Additional findings were a separated clavicle, lacrimal duct stenosis and prenatally detected renal hypoplasia. SNP array results revealed a duplication between 11q13.5 and 11qter, measuring 58 Mb, from nucleotide 76,601,607 to 134,926,021. As a result, molecular karyotyping could be performed in such cases in order to establish a definite phenotype-genotype correlation using conventional or molecular cytogenetics techniques.

First Report of Artichoke yellow ringspot virus in Globe Artichoke in Turkey.

Turkey is one of the main globe artichoke (Cynara cardunculus L. subsp. scolymus (L.) Hayek) producers in the world. Cultivation of this crop is done mainly in the Aegean and Eastern Marmara regions with asexually propagated cultivars such as Bayrampasa and Sakiz. More than half of total globe artichoke production in Turkey is obtained from the provinces of Izmir, Aydin, and Mugla in the Aegean region. Surveys in 2011 and 2012 were carried out to look for the presence of Artichoke yellow ringspot virus (AYRSV), Tobacco mosaic virus (TMV), and Tomato spotted wilt virus (TSWV) in the globe artichoke production areas in these three provinces. Double antibody sandwich (DAS)-ELISA and reverse transcriptase (RT)-PCR assays conducted for TMV and TSWV showed that the samples were not infected with these two viruses. Due to the lack of commercial ELISA kits against AYRSV, RT-PCR and biological indexing were used for its identification. Leaf tissues from 35 symptomatic and 25 symptomless plants were sampled and analyzed by RT-PCR using as template total RNAs extracted by a silica gel method (1). RT-PCR was conducted as previously reported (1). A PCR product of the expected size (about 530 bp) was obtained from five plant samples that were collected from Izmir province and had symptoms of bright yellow spots and line patterns on the leaves. The incidence of diseased plants in the fields ranged from 1 to 5%. In previously conducted studies, these symptoms were defined as typical symptoms of AYRSV on artichokes (2,3,4). One of the PCR products was cloned and sequenced. BLASTn analysis of the obtained sequence (GenBank Accession No. KC622054) showed 92% nucleotide identity with the partial RNA1 sequence of an AYRSV isolate from Allium cepa (AM087671.2). Furthermore, selected test plants were mechanically inoculated with sap from plant samples that were positive in RT-PCR. Chlorotic local lesions and systemic mottling symptoms were observed on Chenopodium quinoa; chlorotic lesions, mosaic, and deformation on Cucumis sativus; and systemic mosaic, reddish necrotic local lesions, and malformation on Phaseolus vulgaris (French bean). Results of the biological tests were confirmed by RT-PCR. AYRSV has a wide host range including artichoke and six other cultivated plant species and can be easily transmitted by seed, plant sap, and vegetative propagation (3). To our knowledge, this is the first report of natural infection of globe artichoke by AYRSV in Turkey. AYRSV infections can have a detrimental effect on the growth and yield of artichoke plantings. This assay will be useful for further epidemiological studies. References: (1) X. Foissac et al. Acta Hortic. 550:37, 2001. (2) D. Galliitelli et al. Adv. Virus Res. 84:289, 2012. (3) P. E. Kyriakopoulou et al. Ann. Inst. Phytopathol. Benaki 14:139, 1985. (4) V. I. Maliogka et al. Phytopathology 96:622, 2006.

Endoscopic ultrasound-guided transluminal drainage of pancreatic duct obstruction: long-term outcome.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided pancreatic drainage (EUS-PD) has been reported as an alternative to surgery, when transpapillary access to the main pancreatic duct (MPD) is impossible. The aim of the study was to investigate the feasibility of the procedure and long-term clinical outcome in patients treated with EUS-PD. PATIENTS AND METHODS: We retrospectively analyzed our single-center experience over a 10-year period. RESULTS: EUS-PD was attempted in 20 patients (24 interventions), with a median age of 64 years (range 36 - 78). Indications for the procedure were post-Whipple symptomatic anastomotic stricture (n = 10) and chronic pancreatitis (n = 10). EUS-PD was performed by a transgastric (n = 16) or transbulbar (n = 3) route or with a rendezvous technique (n = 5). Wirsungography was performed in all interventions and successful drainage was achieved in 18 / 20 (90 %) patients. There were two minor procedure-related complications: bleeding that was treated endoscopically, and a perigastric collection that resolved spontaneously. Median follow up was 37 months (range 3 - 120 months), stent dysfunction occurred in 9 / 18 (50 %) patients. Out of 18 patients with successful EUS-PD, long-term pain resolution was observed in 13 (72 %). At the last follow-up visit, there were significant decreases in pain scores, from 7.5 to 1.6, and in MPD size from 8.1 mm to 3.9 mm. Failure was associated with cancer presence or recurrence. CONCLUSIONS: Technical success rate of EUS-PD and clinical long-term pain resolution were 90 % and 72 %, respectively. EUS-PD is a reliable procedure with a low complication rate. It might therefore replace surgery at expert centers.

Partial deletion of the long arm of chromosome 13 (q32q33.2) associated with mental retardation, choanal atresia and fish mouth.

13q deletion syndrome is characterized by mental and motor retardation, craniofacial dysmorphic facial appearance and various congenital malformations. In this article, we present a new case with 13q deletion syndrome phenotypically characterized by fish mouth, choanal atresia and severe mental and motor retardation. In order to determine the certain localization of deleted region high resolution multicolor-banding technique was performed and the karyotype determined as 46,XX,del(13)(q32q33.2). To come in future to a genotype-phenotype correlation, it is very important to delineate the deleted region in such cases in detail by cytogenetic/ molecular cytogenetic methods.

The case of an infertile male with an uncommon reciprocal X-autosomal translocation: how does this affect male fertility?

Infertility is defined as the inability to conceive after one year of regular unprotected intercourse. Constitutional numerical and/or structural chromosomal aberrations like sex-chromosome aberrations are one of the possible factors involved in fertility problems. Reciprocal translocations between an X-chromosome and an autosome are rarely seen in men. Male carriers of an X-autosome translocation are invariably sterile, regardless of the position of the breakpoint in the X-chromosome. Breakpoints in autosomal chromosomes could also be involved in male infertility. In this paper, we describe a 31-year-old male with azoospermia. GTG banding with high resolution multicolor-banding (MCB) techniques revealed a karyotype 46,Y,t(X;1)(p22.3;q25), and we discuss how the breakpoint of this translocation could affect male infertility. As a conclusion, cytogenetic evaluation of infertile subjects with azoospermia should be considered in the first place before in vitro fertilisation procedures are planned.

Calpain 10 gene single-nucleotide 44 polymorphism may have an influence on clinical and metabolic features in patients with polycystic ovary syndrome.

AIM: This study was designed in order to examine the relationship between Calpain 10 [single-nucleotide polymorphism (SNP) 19,43,44,63] gene polymorphisms and clinical and hormonal characteristics in women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: One hundred and seven patients with PCOS and 114 healthy subjects were included in this study. Serum levels of sex steroids were measured for each individual. Insulin resistance (IR) was evaluated by the homeostasis model assessment (HOMA) and quantitative insulin-sensitivity check index (QUICKI) methods. Insulin and glucose responses to the oral glucose tolerance test (OGTT) were analyzed by calculating the areas under the curve for insulin (AUCI) and glucose by the trapezoidal methods.We used PCR and restriction fragment length polymorphism technique to examine Calpain 10 SNP 19, 43, 44, and 63 polymorphisms. RESULTS: Allele distribution of Calpain 10 SNP 44 gene polymorphism was observed as significantly different between the groups. Calpain 10 SNP 44 TC genotype was found to be increased in PCOS subjects (69.15%) compared to the control subjects (50%). However, when compared to control subjects, patients with PCOS had similar Calpain 10 SNP 19, Calpain 10 SNP 43, and SNP 63 gene polymorphisms. When compared with normal Calpain 10 gene SNP 44 allele in PCOS subjects, subjects with PCOS having Calpain 10 gene SNP 44 allele polymorphism had higher free testosterone, androstenedione, DHEA-S, and fasting insulin levels. Also, PCOS women with Calpain 10 gene SNP 44 allele polymorphism had high Ferriman-Gallwey (F-G) score, acne, prevalence of menstrual disturbances, waist-hip ratio, HOMA-IR, AUCI levels and low QUICKI levels. CONCLUSION: The findings show that Calpain 10 gene SNP 44 allele polymorphism may have a role in PCOS pathogenesis. However, larger-scale studies are needed in this field.