A FURTHER PATIENT OF PURE 15q DELETION: CLINICAL AND MOLECULAR CYTOGENETIC FINDINGS.

A deletion of the distal long arm of chromosome 15 is generally reported with the formation of ring chromosome 15, whereas an isolated 15q deletion is rarely described. Here we report an 11 year-old girl, from non-consanguineous parents, who was referred to the Pediatric Genetics Department with growth retardation and multiple congenital abnormalities. In her medical history, she had a cleft palate, hip dislocation and crossed renal ectopia. Dysmorphological evaluation revealed a triangular face, low-set ears, fissured cleft tongue, micrognathia, proximally placed hypoplastic thumbs, genu valgus, 2-3 toe skin syndactyly, clinodactyly and nail hypoplasia. Speech problems were also noticed. The karyotype was normal. Subtelomeric fluorescent in-situ hybridisation (FISH) analysis showed a de novo terminal deletion about 755 kb. Furthermore, the breakpoint was located within the CHSY1 gene that is responsible for Temtamy preaxial brachydactyly syndrome which shares clinical features with 15qter deletion syndrome. To the best of our knowledge, this deletion is the smallest among reported patients. It is considered that the patient presented here significant contribution to phenotype-genotype correlation in 15q deletion patients.

In vitro gene manipulation of spinal muscular atrophy fibroblast cell line using gene-targeting fragment for restoration of SMN protein expression.

The reduced level of survival motor neuron (SMN) protein, caused by homozygous deletions in the SMN gene, led to a common neurodegenerative disorder known as spinal muscular atrophy (SMA). In spite of extensive efforts to find a cure for SMA, there is currently no effective treatment available for this devastating disease. In this study, restoration of SMN expression through 'gene-targeting' method in SMA fibroblast cells was attempted. We designed a 2697-bp gene-targeting cassette; it consisted of an SMN1 open reading frame expressing 38 kD SMN protein and the upstream and downstream regions of exon 1 of SMN1 gene at the ends as the homology arms. SMA fibroblast cells were transfected by gene-targeting cassette using Lipofectamine LTX-PLUS reagent. Occurrence of homologous recombination in selected cells was investigated by PCR analysis. Increased expression of SMN protein was shown by real-time PCR and western blotting analysis. The immunofluorescence analysis results demonstrated that the number of SMN nuclear structures, Gems, was the same as or greater than the number of Gems found in normal fibroblasts. The results of this study indicate that gene-targeting methods do, in fact, present as an alternative for restoration of SMN expression in SMA patients-derived cells in vitro.

EVALUATION OF PREIMPLANTATION GENETIC ANEUPLOIDY SCREENING CASES AT A REFERENCE GENETICS CENTER: 10 YEARS' EXPERIENCE.

The aim of this study is to review and evaluate our preimplantation genetic screening (PGS) records in terms of their demographic data, indications, cytogenetic results, pregnancy outcomes and discuss these findings in different aspects. PGS was performed in a total of 84 couples (87 cycles) between the period 2005 to 2015. Biopsied blastomeres from embryos on day 3 were fixed and fluorescence in situ hybridization was carried out for chromosomes 13, 16, 18, 21, 22, X and Y depending on the indication. The diagnostic and clinical data were retrospectively evaluated. A total of 450 blastomeres were biopsied. Ninety-eight of them were found to be suitable for transfer. They were transferred to 72 patients in 75 cycles resulting in 23 pregnancies and 20 healthy births. The most common indication was unexplained infertility. The implantation rate was calculated as 23.4% whereas the take-home baby rate was 26.6% per transfer. The highest rate of healthy living births is achieved in patients having low grade maternal mosaic sex chromosomal aneuploidy. All living births achieved by PGS had normal chromosomal structure which we can propose it as an alternative test for couples at risk to select normal embryos to improve the outcomes of assisted reproductive procedures and to avoid the transfer of chromosomally unbalanced and multiple embryos.

Genome-wide copy number variation analysis in idiopathic intellectual disability/multiple congenital anomalies.

New array technologies have facilitated the analysis of submicroscopic chromosomal imbalances and structural variants. Copy number variation (CNV) analysis can reveal genetic imbalances in up to 10% of cases involving intellectual disability (ID), with or without multiple congenital anomalies (MCA). Here we present 4 cases, diagnosed by CNV analysis using Affymetrix Genome Wide Human SNP 6.0 array, and their parents. CNVs ranging from 18 to 196 per subject, with a size range of 100kb- 6093kb, were detected in all cases. One case revealed inherited CNVs, whilst de novo ins/dels were found in the other three which may be causative factors in the development of clinical pictures. Microarray technology may help to reveal the etiology of ID and is a potentially useful diagnostic tool for patients with ID/MCA.

Efficacy of the cardiac rehabilitation program in patients with end-stage heart failure, heart transplant patients, and left ventricular assist device recipients.

OBJECTIVE: The objective of this study was to assess the effects of cardiac rehabilitation on the functional capacity, pulmonary functions, quality of life, and psychological state of patients who had heart failure (HF), heart transplantation (HTx), or a left ventricular assist device (LVAD). METHODS: An 8-week exercise program was undertaken by 46 patients diagnosed with end-stage heart failure, 40 of whom had a heart transplantation and 11 were implanted with an LVAD. The patients' functionality was assessed with a maximal oxygen consumption test (pVO2), their psychological state with the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI), their quality of life (QOL) with the Short Form 36 (SF 36), and their pulmonary condition with pulmonary function tests (PFTs). RESULTS: A significant improvement was observed in all forced vital capacity (%), forced expiratory volume in 1 second (%), pVO2, BDI, and most of the subscores of the SF 36 scores at the end of the exercise, compared with the pre-exercise period (P < .05). The intergroup evaluations showed no significant differences among the 3 groups in terms of all assessed changes (P > .05). CONCLUSION: An 8-week supervised exercise program was observed to improve functional capacity, PFT, QOL, and depression among patients who had HF, HTx, or LVAD. Supervised exercise should be recommended for every patient included in a heart transplant program.

Subtelomeric rearrangements in patients with idiopathic intellectual disabilitiy/ multiple congenital anomalies and recurrent miscarriages: seven years' experience.

Cryptic subtelomeric anomalies are a significant cause of idiopathic intellectual disability and/or multiple congenital anomalies (ID/MCA) and multiple miscarriages (MM). Effective preselection of patients is essential as the cost of subtelomeric testing is high and it is labor-intensive. Therefore, the aim of this study is to evaluate the frequency of subtelomeric anomalies by using commercial FISH probes in 151 patients of ID/MCA and 32 couples with MM who were referred to a genetic center during 7-year period and to determine whether performing subtelomeric testing is feasible for these groups of patients. We assessed the clinical information of all referrals including family history, physical examination, facial dysmorphism, congenital malformations and scored the ID/MCA patients according to the criteria suggested previously. The etiology was not elucidated and all patients had normal karyotypes. Subtelomeric deletions were found in 10 patients in ID/MCA group (6.62%). These were deletions of 14qter (2 patients), 18qter (2 patients), 18pter (2 patients), 15qter, 7pter, 8pter and 4qter. The clinical information of all patients having deletions has been summarized and confined with the current literature. No anomaly was detected in the MM group. In conclusion, the prevalence of subtelomeric anomalies in ID/MCA group in this study is consistent with the literature and subtelomeric FISH analysis is feasible in determining their etiology when a checklist is used. Besides, assessment of the genetic basis of ID/MCA had lead the prevention of the recurrence of such conditions in selected families as well as elucidating novel genetic causes of ID.

Partial trisomy 2p24-->pter and monosomy 18q22.1- qter resulting from parental translocation.

This is a report of a 6 month-old boy with a partial trisomy 2p24-->pter and monosomy 18q22-->qter. This is the first case presenting this unbalanced translocation with phenotypic features. The patient had growth and developmental retardation, facial dysmorphism, cleft palate, congenital cardiopathy, hypospadias, evantration of diaphragm and deafness. Cranial MRI showed mild ventricular dilatation. Cytogenetic analysis of the patient and his parents revealed a karyotype 46,XY, der(18), t(2;18)(p24;q22)mat in the patient. Subtelomeric FISH analysis confirmed the cytogenetic findings. Phenotypic features were consistent with either partial trisomy 2p or deletion 18q.

Translation and validation of the Turkish version of the Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire.

The Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire is a disease-specific measure of needs-based quality of life developed in the UK and the Netherlands. This study describes translation, validation, and reliability of the scale into Turkish population. The ASQoL was translated into Turkish using the dual-panel process. Content validity was assessed via cognitive debriefing interviews with ankylosing spondylitis (AS) patients. Patients with AS according to modified New York criteria were recruited into the study from 12 hospitals of all part of Turkey. Psychometric and scaling properties were assessed via a two administration survey involving the ASQoL, the Nottingham Health Profile (NHP), Bath AS Functional Index (BASFI), and Bath AS Disease Activity Index (BASDAI). Classical psychometrics assessed reliability, convergent validity (correlation of ASQoL with NHP, BASFI, and BASDAI) and discriminative validity (correlation of ASQoL with perceived AS-severity and general health). Cognitive debriefing showed the new Turkish ASQoL to be clear, relevant, and comprehensive. Completed survey questionnaires were received from 277 AS patients (80% Male, mean age 42.2/SD 11.6, mean AS duration 9.4 years/SD 9.4). Test-retest reliability was excellent (0.96), indicating low random measurement error for the scale. Correlations of ASQoL with NHP sections were low to moderate (NHP Sleep 0.34; NHP Emotional Reactions 0.83) suggesting the measures assess related but distinct constructs. The measure was able to discriminate between patients based on their perceived disease severity (p < 0.0001) and self-reported general health (p < 0.0001). The Turkish version of ASQoL has good reliability and validity properties. It is practical and useful scale to assess the quality of life in AS patients in Turkish population.

A new clinical presentation associated with pontine clefting, hyperpigmentation and short stature in addition to craniofacial, cardiac and developmental anomalies.

We report on a 13-year-old girl who was the first child of nonconsanguineous parents, and who suffered from short stature accompanied with mental retardation, generalized hyperpigmentation of the skin and craniofacial findings. Her cardiological examination revealed atrial septal defect, mitral valve prolapsus and atrial septal aneurysm. Brain scans revealed dilatation of the third and lateral ventricles and a pontine cleft. Growth hormone (GH) deficiency was observed during the evaluation of GH/IGF-I axis. All the laboratory tests performed including metabolic screening, conventional karyotype and oligonucleotide array were normal. Mutation analysis of the C2ORF3 7 gene revealed no mutation. The clinical signs seen in this patient likely represent a new dysmorphological syndrome which has not been previously described.

Oculocerebral hypopigmentation syndrome maps to chromosome 3q27.1q29.

BACKGROUND: In 1967, Cross et al. [J Pediatr 1967;70:398-406] reported four siblings with intellectual disability, microcephaly, neurologic and ocular disorders, and hypopigmentation involving skin and hair. This novel entity, known as oculocerebral hypopigmentation syndrome (OCHS) or Cross syndrome (OMIM 257800), is assumed to be autosomal recessive. However, its genetic cause is still unknown. CASE REPORT: A 4-year-old girl is reported with OCHS, a history of recurrent infections and vertebral fusion of L4-L5. Central nervous system and cardiac imaging as well as metabolic screening were normal. Microscopic hair investigations did not show any melanin deposit defects. RESULTS: Using molecular cytogenetics, we detected a de novo interstitial del(3)(q27.1q29) of the paternal chromosome. To our knowledge, this is the first molecular genetics finding in a patient with OCHS. Here we discuss the genotype-phenotype correlations and suggest candidate genes for this disorder. CONCLUSION: Investigating further patients would enable fine-mapping the OCHS locus and identifying its putative gene.

Unusual presentation of biliary atresia splenic malformation syndrome with autosomal dominant hypospadias.

Biliary atresia is associated with polysplenia in 2-10% of cases and is defined as Biliary Atresia Splenic Malformation syndrome (BASM). The main features of BASM syndrome include extrahepatic biliary atresia and polysplenia besides the characteristic findings of laterality anomalies, cardiac anomalies, intraabdominal vascular anomalies, pancreatic anomalies and malrotation. Here we present a 6-month-old male patient with BASM having atrial septal defect, umblical hernia, inguinal hernia, and hypospadias. Clinical history revealed that his father also had hypospadias which showed a rare form of autosomal dominant inheritance. The karyotype was normal and the molecular analysis of CFC1 gene revealed no mutation. We emphasize the importance of a detailed physical examination in cases with BASM.

Interobserver and intraobserver reliability in lower-limb flexibility measurements.

AIM: To describe the inter- and intraobserver reliability of lower extremity flexibility tests, and to explore the effect of sports activity on the results. METHODS: A total of 66 subjects consisting of 20 professional athletes, 26 active subjects performing any sporting activity and 20 control subjects were included. Various flexibility tests were performed to determine hamstring, quadriceps and hip adductor muscle flexibility by two examiners blinded to each other for interobserver reliability. Intraobserver reliability of tests were evaluated by one the examiners 1 week later. Inter- and intraobserver reliability was analyzed with intraclass correlation coefficient (ICC), coefficient of variation (CV) and critical difference (CD). RESULTS: ICC analysis showed that inter- and intra-observer reliability results were satisfactory for all measurements. Athletes performed the best results of inter- and intraobserver reliability for flexibility tests in means of CV and CD compared with active and control groups (P<0.05). Popliteal angle measurement was the most reliable one among hamstring flexibility tests where as the least reliable test was chair sit and reach test in all groups. CONCLUSION: This is the first study evaluating extensively the reliability of flexibility tests in different intensities of sports activity. Flexibility measurements of quadriceps and hip adductor muscles can be used reliably in clinical practice as hamstring flexibility tests. The intensity of performed activity may have an effect on the reliability of flexibility tests.

Does pretransplantation etiology have any effect on exercise results in heart transplant patients?

OBJECTIVE: The objective of this study was to analyze the effect of pre-transplantation etiology and post-transplantation exercise on pulmonary function tests, functional capacities, psychological symptoms and quality of life among heart transplant patients. METHODS: An eight-week exercise program was applied to 35 heart transplant patients with histories of ischemic heart failure (HF; n = 20) or dilated HF (n = 15). All patients were evaluated before and after exercise in terms of breathing function tests, functional capacity (FVC; maximal oxygen consumption, pVO2), psychological symptoms (Beck Depression Scale (BDS), Spielberger's State-Trait Anxiety Inventory (STAI)) and quality of life (Short Form 36, SF-36). RESULTS: At the end of the exercise compared to the pre-exercise period significant improvements were observed in all FVC%, FeV1%, FeV1/FVC%, pVO2, SF 36 scores reflecting physical function, physical role, pain, general health, vitality, social function, and emotional role (P < 0.05) among heart transplant patients who were operated due to ischemic or dilated heart failure. In contrast, no significant improvement was observed in the BDS and STAI scales (P > 0.05). There was no significant etiology-related difference between the groups in terms of the evaluated parameters (P > 0.05). CONCLUSION: We demonstrated improvements in function tests, functional capacity and quality of life for both ischemic and dilated heart transplant patients following a supervised exercise program. We concluded that the positive effect achieved by exercise was not related to pre-transplantation etiology. Whatever the preoperative etiology, a regular exercise program is recommended for heart transplant patients in the rehabilitation unit.

Long-term evaluation of chromosomal breakages after radioisotope synovectomy for treatment of target joints in patients with haemophilia.

Radioisotope synovectomy (RS) is defined as the intra-articular injection of radioisotopic agents with the aim of fibrosis on hypertrophic synovium in the target joint. The aim of this study was to investigate genotoxic effects on lymphocytes and malign transformation induced by Yttrium(90) (Y(90)) and Rhenium(186) (Re(186)) in children with haemophilia undergone RS. Forty haemophilia patients were enrolled. The mean age was 16.4 +/- 6.2 years (range: 8-40). Y(90) was used for knees, Re(186) was used for other joints. For safety, cytogenetic analysis was performed to determine potential chromosomal changes after RS procedure at three different time points as prior to procedure, 3rd day and 90th day. For the stimulation of chromosomal breakages, diepoxybutane was used (DEB test). Chromosomal breakages (CBs) were found in 23 patients (67.6%) prior to RS. We have found CBs additionally in nine of 11 patients who had no CBs prior to RS after 3 days of radioisotope exposure. At that time, the patients who had CBs were 29 (85.2%). At day 90, only 21 patients revealed (61.7%) CBs. The mean frequency of CBs slightly but not significantly increased in the 3rd day. However, there was a significant decreasing trend between 3rd and 90th days. Radioisotope synovectomy with Y(90) and Re(186) does not seem to induce the genotoxic effects significantly on peripheral blood lymphocytes. However, CBs even after one year in the re-evaluation of four patients, significant decrease in the number of CBs between the 3rd and 90th days and de novo CBs after exposure may be accepted as warning signals for young population. It should also be pointed out that families and patients be informed properly related with historical and potential dangers of radioisotopic agents.

Effects of pilates exercises on functional capacity, flexibility, fatigue, depression and quality of life in female breast cancer patients: a randomized controlled study.

BACKGROUND: There are very few randomized controlled studies on exercise in cancer patients. Consequently, there are no guidelines available with regard to the exercises that can be recommended and difficulties are encountered in the clinical practice as to which exercise is more suitable to the patients. AIM: The purpose of this study was to investigate the impact of pilates exercises on physical performance, flexibility, fatigue, depression and quality of life in women who had been treated for breast cancer. DESIGN: Randomized controlled trial. SETTING: Out patient group, Department of Physical Medicine and Rehabilitation and Medical Oncology Department, University Hospital. POPULATION: Fifty-two patients with breast cancer were divided into either pilates exercise (group 1) and control group (group 2). METHODS: Patients in Group 1 performed pilates and home exercises and patients in group 2 performed only home exercises. Pilates exercise sessions were performed three times a week for a period of eight weeks in the rehabilitation unit. MAIN OUTCOME MEASURES: Subjects were assessed before and after rehabilitation program, with respect to, 6-min walk test (6MWT), modified sit and reach test, Brief Fatigue Inventory (BFI), Beck Depression Index (BDI) and the European Organisation for Research and Treatment of Cancer Quality of Life C30 (EORTC QLQ-C30) and EORTC QLQ BR23. RESULTS: After the exercise program, improvements were observed in Group 1 in 6-minute walk test, BDI, EORTC QLQ-C30 functional, and EORTC QLQ-C30 BR23 functional scores (P<0.05). In contrast, no significant improvement was observed in Group 2 after the exercise program in any of parameters in comparison to the pre-exercise period (P>0.05). When the two exercise groups were compared, there were significant differences in 6MWT in pilates-exercise group (P<0.05). CONCLUSION: Pilates exercises are effective and safe in female breast cancer patients. There is a need for further studies so that its effect can be confirmed. CLINICAL REHABILITATION IMPACT: This study addressed the effects of pilates exercise, as a new approach, on functional capacity, fatigue, depression and quality of life in breast cancer patients in whom there are doubts regarding the efficacy and usefulness of the exercise.

The frequency of fibromyalgia syndrome and quality of life in hospitalized cancer patients.

To explore the frequency of fibromyalgia syndrome (FMS) among hospitalized cancer patients and address the relationships between pain, fatigue and quality of life with regard to the extent of pain, a cross-sectional and descriptive study was carried out in the Oncology Supportive Care Unit on 122 hospitalized cancer patients. Pain, sleep, disease impact (Fibromyalgia Impact Questionnaire), fatigue (Brief Fatigue Inventory), quality of life (Short Form 36 and European Organization for Research on Treatment of Cancer questionnaires Quality of Life-C30) were gathered using standardized measures. Thirteen of the hospitalized cancer patients (10.7%) included in the study were diagnosed with FMS. There were no statistically significant differences among three pain groups with respect to demographic characteristics (P > 0.05). There were significant differences among groups with regard to the presence of metastasis, fatigue, sleep disorder, pain, Brief Fatigue Inventory, Fibromyalgia Impact Questionnaire, most of subscores of Short Form 36 and European Organization for Research on Treatment of Cancer questionnaires Quality of Life-C30 scores (P < 0.05). In the present study, we have calculated the frequency of FMS among patients admitted to the oncology hospital in addition to establishing the relationships between pain, fatigue and quality of life with regard to the extent of pain. We believe that the descriptive data presented in this study would be helpful in future studies and therapeutic approaches.

Isokinetic muscle strength for ankle extensors and flexors: a comparison between elite sprint runners and swimmers.

AIM: The aim of this study was to evaluate through isokinetic tests the muscular condition of ankles of elite sprint swimmers and elite sprint runners, and make comparisons within these groups. METHODS: Fourteen elite swimmers and 8 elite runners were included in this cross-sectional study. The ankle extensors and flexors strength characteristics of elite sprinter athletes were tested at a slow (30 degrees/s) and a fast (120 degrees/s) speed using an isokinetic dynamometer. Subjects were assessed by one examiner on six separate days, within a 2-week period. RESULTS: A significant difference was noted between right and left sides for ankle joint flexors in runners at slow speed. Runners had higher left ankle flexion measures at 30 degrees/s and 120 degrees/s angular velocity than swimmers. There was no significant difference between the peak torques of the left and right sides at all angular velocities in swimmers. CONCLUSION: To our knowledge, this is the first study to assess the ankle flexors and extensors strength characteristics of elite sprinter swimmers making a comparison with elite sprinter runners. The findings presented in this study report the sport specific difference between the sprint swimmers and sprint runners. These values add a quantative dimension to rehabilitative and preventive sports medicine for elite sprinter runners and swimmers.

Complex regional pain syndrome in a patient with spinal cord injury: management with pulsed radiofrequency lumbar sympatholysis.

STUDY DESIGN: Short communication. OBJECTIVES: To report a case with bilateral lower extremity complex regional pain syndrome (CRPS) in a patient with paraplegia occurring following spinal disc herniation surgery, who was treated successfully with pulse radiofrequency (PRF) lumbar sympatholysis. SETTING: Departments of Physical Medicine and Rehabilitation, Algology Department of Anaesthesiology and Nuclear Medicine, Medical Faculty of Ege University, Izmir, Turkey. METHODS: A 55-year-old woman had neuropathic pain in her lower extremities after T12-L1 disc herniation surgery. The pain decreased to a tolerable level with conservative treatment and her condition remained stable for the following 6 months; then she developed swelling, redness and severe burning pain in both feet. Physical examination showed edema and redness in the feet. On the basis of clinical findings and Tc-99m methylene diphosphonate (MDP) three-phase bone scintigraphy, she was diagnosed to have CRPS. RESULTS: The patient underwent a diagnostic sympathetic ganglion blockade with bupivacaine, which resulted in a marked decrease in the pain and edema of the feet. Consequently, PRF lumbar sympatholysis was performed with a successful outcome in pain, edema and color changes in the feet. CONCLUSION: When treatment of CRPS fails with conventional modalities, PRF sympatholysis may be used for control of pain and other symptoms in such patients.