A novel homozygous SLC12A3 mutation causing Gitelman syndrome with co-existent autoimmune thyroiditis: a case report and review of the literature.

Gitelman syndrome is a rare, autosomal recessively inherited tubulopathy manifesting with hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Common symptoms include fatigue, myalgia, reduced performance capacity, tetany, paresthesia, and delayed growth. However, as reported in the literature, diagnosis in some patients is prompted by an incidental finding of hypokalemia. GS develops due to mutations in the SLC12A3 gene, which encodes the thiazide-sensitive Na-Cl cotransporter. Many variants in the SLC12A3 gene causing GS have been reported in literature. A new pathogenic homozygous mutation (c.2612G > T), absence of hypomagnesemia, and accompanying autoimmune thyroiditis are remarkable in our patient. There are a few Gitelman syndrome cases that are complicated with autoimmune thyroiditis in the literature. In this study, we present a case of Gitelman syndrome with a novel homozygous mutation and accompanying autoimmune thyroiditis and review of the literature.

A new perspective on isotretinoin in pregnancy: Pregnancy outcomes, evaluation of complex phenotypes, and importance of teratological counselling.

OBJECTIVES: Teratogens are responsible for 5% of all known causes of congenital anomalies. Isotretinoin, a retinoic acid-derived agent, leads to congenital anomalies in 21-52% of cases when exposure occurs during pregnancy according to studies conducted before 2006. However, rates of congenital anomalies were much lower in later studies. The purpose of this study was to investigate the rates of congenital anomalies in isotretinoin exposure during pregnancy, isotretinoin exposure before pregnancy, and a control group unexposed to any teratogenic agents. STUDY DESIGN: In this cohort study, we divided pregnant women admitted to our center between 2009 and 2020 into two groups: isotretinoin exposure before and during the pregnancy (n = 77) and isotretinoin exposure before the pregnancy (n = 75). We selected the control group from among the non-teratogen exposed pregnant women with a simple random sampling method. Obstetricians calculated the ages of all pregnancies via ultrasound (USG) (crown-rump diameter for the first trimester; biparietal diameter and femur length for the second trimester). After birth, a pediatric genetics specialist examined all babies. Whole-exome sequencing (WES) was conducted on the babies who displayed complex phenotypes. RESULTS: Among the isotretinoin exposure before and during the pregnancy, isotretinoin exposure before the pregnancy, and the control groups, there were statistically significant differences in live births (respectively, 64.3 %, 88 %, 93.3 %), congenital anomalies (respectively, 28.6 %, 6.1 %, 1.4 %), miscarriages (respectively, 13 %, 2.7 %, 4 %), terminations (respectively, 32.5 %, 9.3 %, 2.7 %), and premature births (11.9 %, 16.7 %, 2.9 %) (respectively, p < 0.001, p < 0.001, p = 0.014, p < 0.001). We detected novel phenotypical features in five patients. CONCLUSIONS: Our study demonstrated that study design, long-term follow-up, teratological counseling, and implementation of advanced molecular analysis in complex phenotypes with novel phenotypical features are beneficial for understanding the association of congenital anomalies with isotretinoin exposure. While evaluating congenital anomalies, we detected statistically significant differences between isotretinoin exposure before and during the pregnancy vs control, but we did not detect any statistically significant differences between isotretinoin exposure before the pregnancy and controls. Another finding of the study is that WES might be an efficient way to evaluate complex phenotypes in isotretinoin-exposed babies; however, further research is required.

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.

Should chromosomal analysis be performed routinely during the baseline evaluation of the gender affirmation process? The outcomes of a large cohort of gender dysphoric individuals.

The role of genetics in the etiology of gender dysphoria (GD) is an important yet understudied area. Yet whether genetic analysis should be carried out during the gender affirmation process at all is a matter of debate. This study aims to evaluate the cytogenetic and molecular genetic findings of individuals with GD. We retrospectively reviewed the medical records of individuals with GD who were followed up in a tertiary clinic. After the exclusion criteria were applied, the study sample consisted of 918 individuals with GD; 691 of whom had female-to-male (FtM) and 227 male-to-female (MtF) GD. The cytogenetic analysis revealed that 223 out of 227 (98.2%) individuals with MtF GD had the 46,XY karyotype, while 683 out of 691 (98.8%) individuals with FtM GD had the 46,XX karyotype. In the Y chromosome microdeletion analysis, azospermic factor c (AZFc) deletion was detected in only two individuals with MtF GD. Our findings suggest that there are few chromosomal abnormalities in individuals with GD. Thus, this research calls into question both the role of chromosomal abnormalities in GD etiology and why the application of chromosomal analysis is in Turkey a routine part of the baseline evaluation of GD.

Pigmentary retinopathy with perivascular sparing in a SOFT syndrome patient with a novel homozygous splicing variant in POC1A gene.

PURPOSE: SOFT syndrome is an extremely rare inherited dwarfism syndrome. The syndrome has four major clinical manifestations: short stature, onychodysplasia, facial dysmorphism, and hypotrichosis. Herein, we report a unique case of a SOFT syndrome with findings of pigmentary retinopathy. METHODS: Case report. RESULTS: A 3-year boy was referred to our clinic for ophthalmologic examination from Genetic Diseases Diagnosis Center. In ophthalmic examination, anterior segment was normal bilaterally in biomicroscopy. Fundus examination revealed bilateral yellow-white punctate retinal pigment epithelium lesions located in the midperipheral retina. Macula optical coherence tomography was bilaterally normal. Whole exome sequencing (WES) analysis revealed a homozygous intronic splice site variant (c.103 + 1 G>T) in POC1A, hemizygous intronic splice site variant (c.459-5T>A) in TBX22, and a heterozygous missense variant (c.2254 C>T) in DDR2 genes. CONCLUSION: There is a limited number of reported cases with SOFT syndrome and, though retinal findings in SOFT syndrome have been reported in two cases previously, none were given in detail. According to our findings, perivascular and macula sparing midperipheral retina pigment epithelium changes could be observed in patients with SOFT syndrome.

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.

Isolated abducens nerve palsy due to COVID-19.

Although coronavirus disease-2019 (COVID-19) is mainly a respiratory system disease, neurological complications due to peripheral and central nervous system involvement may be seen in these patients. In this case report, we described a patient with isolated abducens nerve palsy after COVID-19. The patient was a healthy 28-year-old man who developed isolated abducens nerve palsy 10 days after COVID-19. He had no systemic risk factors. He had 20 PD left esotropia (ET) at distance and 16 PD left ET at near in primary position and ET increasing to 25 PD in left gaze. He had left abduction deficiency. His cranio-orbital magnetic resonance imaging findings were normal. He was diagnosed as left isolated abducens nerve palsy and his findings were recovered after 2 months. COVID-19 may cause ocular motor nerve palsies. Although the pathological mechanism remains unclear, direct viral invasion, inflammatory and immune mechanisms may play role. Further case reports and studies are needed to support these findings.

Co-existing bipolar disease and 17q12 deletion: a rare case report.

BACKGROUND: 17q12 microdeletion syndrome is a rare autosomal dominant chromosomal anomaly, caused by the deletion of a 1.4 Mb-spanning DNA sequence on the long arm of chromosome 17. Herein, we report the first bipolar disease (BPD) case with a 1.6-Mb deletion in the 17q11.2-17q12 chromosome region. MATERIALS AND METHODS: Physical examination of the case was performed. Karyotype and microarray analyses were performed for the case and the parents. RESULTS: Physical examination revealed mild dysmorphic features such as high and forehead, full cheeks, slightly depressed nasal bridge and arched eyebrow. Chromosomal analysis of the patient revealed 46, XX, del(17)(q12) karyotype, and parents' karyotype were normal. In the microarray analysis of patient, 1.6 megabases deletion was detected in the 17q12 region [arr(hg19) 17q12 (34,611,352-36,248,918) ×1]. The microarray analysis of the mother was normal. The father's microarray showed 473 kilobases duplication in the 11p11.12 region. CONCLUSION: Although 17q12 deletion syndrome has been associated with bipolar disorder, very few such cases have been described in the literature. Genetic counseling should be considered in patients with remarkable phenotype, complex symptomatology, neurodevelopmental disorder and additional conspicuous medical conditions.

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.

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.

Diplopia due to acquired Brown syndrome after COVID-19 infection.

Coronavirus disease 2019 (COVID-19) is a multisystem, inflammatory condition usually presenting with respiratory symptoms, such as fever, shortness of breath, and severe cough. It may also present with ocular, neurological, and musculoskeletal manifestations. However, since the emergence of the disease in 2019, only a few cases with ocular involvement have been reported in the literature. We present a case of acquired Brown syndrome secondary to COVID-19.

A rare case of an NLRP12-associated autoinflammatory disease.

Pathogenic variants in nucleotide-binding oligomerization-like receptor protein 12 (NLRP12) have been recently suggested as possible causes of autoinflammatory syndromes and should be considered for the differential diagnosis in the patients presenting with symptoms of autoinflammatory diseases. Here we report a very rare case of NLRP12-associated autoinflammatory disease patient who initially presented with polyarthritis and was diagnosed as FMF. Later, the genetic analysis excluded many autoinflammatory conditions including FMF and revealed a c.1206C>G; p.(Phe402Leu) variant in the NLRP12 gene. Awareness of rare autoinflammatory conditions is important to have the best approach to the patients presenting with common symptoms of autoinflammatory diseases.

Assessment of Fetal Rhesus D and Gender with Cell-Free DNA and Exosomes from Maternal Blood.

The detection of fetal cell-free DNA (cfDNA) from maternal plasma has enabled the development of essential techniques in prenatal diagnosis during recent years. Extracellular vesicles including exosomes were determined to carry fetal DNA fragments. Considering the known difficulties during isolation and stability of cfDNA, exosomes might provide a new opportunity for prenatal diagnosis and screening. In this study, comparison of cfDNA and exosome DNA (exoDNA) for predicting the fetal sex and Rhesus D (RHD) genotype was performed by using real-time polymerase chain reaction with simultaneous amplification of sequences of SRY and RHD genes. Fetal sex and RHD were determined in 100 and 81 RHD-negative pregnant women with cfDNA and exoDNA, respectively. The gestation ages of pregnant women were between 9 and 40 weeks. The results were compared with the neonatal phenotype for gender and a serological test for RHD. The cfDNA revealed 95.75% sensitivity and 100% specificity in RHD positivity and 100% sensitivity and 95.45% specificity in SRY positivity. Cohen's agreement coefficient in the Kappa test ranged from 0.8 to 1.0 (P < 0.00001). Although the exoDNA failed to amplify 16 cases, the remaining 65 cases revealed a true estimate for both fetal RHD and SRY genes with 100% sensitivity and specificity. Successful application of exoDNA and cfDNA with real-time PCR for fetal genotyping enables this technique to be applied in the assessment of fetal RHD and gender during pregnancy, allowing initiation of early treatment methods and avoiding unnecessary interventions and cost.

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.

The relation between ankle morphology and osteochondritis dissecans of talus.

The purpose of this study is to describe, if there is, any relation between ankle morphology and development of talus osteochondritis dissecans (OCD) using certain morphological parameters derived from high resolution magnetic resonance imaging (MRI). Study included a total of 93 patients: 26 patients with traumatic medial talus OCD, 30 patients with idiopathic medial talus OCD and 37 patients with normal ankle as the control group. Five MRI morphological parameters (Maximal Tibial Thickness (MTiTh), Malleolar Width (MalW), Length of Trochlea Tali Arc (TaL), Height of Trochlea Tali Arc (TaH) and Angle of Trochlea Tali Inclination (TaIA)) that are expected to be relevant to talus OCD formation are measured and compared for the three groups. Significant difference was found between the idiopathic and the traumatic group in terms of age and gender. Two of five morphologic parameters (MalW and TaL) also showed significant difference for the traumatic and idiopathic group compared to healthy volunteers. Two morphologic parameters that were found to be significantly different from healthy controls may suggest that ankle morphology be a possible factor for talus OCD. Age and gender difference between the traumatic and idiopathic group also may point out different underlying mechanisms for OCD formation.

The Effect of PAI-1 Gene Variants and PAI-1 Plasma Levels on Development of Thrombophilia in Patients With Klinefelter Syndrome.

Klinefelter syndrome (KS) is a common sex chromosome-related abnormality seen among men. KS negatively affects spermatogenesis and testosterone production. It increases the risk of thrombosis but its molecular mechanism has not been well described yet. Elevated PAI-1 is a risk factor for thrombosis. The rs1799889 polymorphism located in the promoter region of the PAI-1 gene was detected in patients with deep venous thrombosis. In this study, the PAI-1 gene variant and its plasma levels in KS patients were examined. Forty-one KS patients (47, XXY) and 50 age-matched healthy controls participated. DNA was isolated from peripheral blood and a real-time PCR method was used to detect known SNPs in the PAI-1 gene. In addition, PAI-1 plasma levels were measured by using ELISA method. There was no significant difference between PAI-1 gene polymorphisms of KS patients and controls ( p > .05). The significant difference was observed in PAI-1 plasma levels between two groups (high PAI-1 plasma level in KS patients compared to controls). The patients' group mean was 55.13 and control group mean in PAI-1 level was 29.89 ng/ml ( p = .020). Clinical features related to thromboembolism especially varicose veins were detected in KS patients frequently ( p = .04). These results suggest that thromboembolism related to clinical features is seen more frequently in cases with KS, but it may not be dependent only on the PAI-1 gene polymorphism structure.

Three novel mutations in 20 patients with hereditary spastic paraparesis.

Hereditary spastic paraparesis (HSP) constitutes both genetic and clinically heterogeneous group of upper motor neuron diseases. Half of the individuals with autosomal dominant (AD) HSP have mutations in SPAST, ATL1, and REEP1 genes. This study was conducted to elucidate the genetic etiology of patients with the pure type AD-HSP diagnosis. The patient group consisted of 23 individuals from 6 families in Turkey. In the first step of work, Sanger sequencing (SS) was performed in ATL1, SPAST, and REEP1 genes and the second phase whole-exome sequencing (WES) was performed following SS analysis for the patients with no detected mutations in these genes. The results of this study revealed that in ATL1, 6 patients have previously reported c.776C > A mutation and 6 patients have novel c.470 T > C mutation. In SPAST, 3 patients have novel c.1072G > C mutation and 2 patients have novel c.1099-1G > C mutation. WES was performed in three patients, who had no detected mutation in these genes with SS analysis. In this approach, as previously reported c.1859 T > C mutation in KIAA0196 was detected, and it was confirmed with the patient's relatives by SS. In three of patients, no HSP-associated variant could be identified in SS and WES. With this study, the molecular genetic etiology in 20 of 23 (87%) individuals that were included in this study with the utilization of SS and WES was elucidated. Utilization of SS and WES methods have enabled the identification of genetic etiology of HSP further with appropriate genetic counseling that was provided to the patients.

A randomized-controlled trial of prolotherapy injections in the treatment of plantar fasciitis.

OBJECTIVES: This study aims to evaluate the efficacy of prolotherapy injections for the treatment of plantar fasciitis. MATERIAL AND METHODS: Between October 2014 and October 2015, 60 patients with symptomatic chronic plantar fasciitis were randomly divided into two groups, as control (n=31) and prolotherapy (n=29) groups. In the prolotherapy group, ultrasound-guided prolotherapy injections into the plantar fascia up to five different points were performed three times every 21 days. In the control group, the patients received instructions for plantar fascia and Achilles tendon stretching exercises three times a week for three months. Additionally, all patients were given heel lifts and instructed to refrain from heavy loading activity. The patients were evaluated via the Visual Analog Scale (VAS), Food and Ankle Outcome Score (FAOS), and Foot Function Index (FFI) at baseline and at 21, 42, 90, and 360 days during follow-up. RESULTS: A total of 50 patients completed follow-up (26 patients in the prolotherapy group and 24 patients in the control group). The VAS, FAOS, and FFI scores were significantly improved in both groups (p<0.001). There were no statistically significant differences in the pain and functional scores at 21 days of treatment between the groups. The VAS and FAOS scores were higher in the prolotherapy group than the control group at 42, 90, and 360 days of treatment. The FFI scores were also higher in the prolotherapy group than the controls at 42 and 90 days of treatment; however, both groups had similar scores at 360 days. CONCLUSION: Our study results suggest that prolotherapy is an effective auxiliary method for treating chronic plantar fasciitis.