The real-world outcomes of Lutetium-177 PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer: Turkish Oncology Group multicenter study.

Metastatic castration-resistant prostate cancer (mCRPC) remains a challenging condition to treat despite recent advancements. This retrospective study aimed to assess the activity and tolerability of Lutetium-177 (Lu-177) PSMA-617 radioligand therapy (RLT) in mCRPC patients across multiple cancer centers in Turkey. The study included 165 patients who received at least one cycle of Lu-177 PSMA-617 RLT, with the majority having bone metastases and undergone prior treatments. Prostate-specific antigen (PSA) levels were assessed before each treatment cycle, and the biochemical response was evaluated in accordance with the Prostate Cancer Work Group 3 Criteria. The PSA decline of ≥50% was classified as a response, while an increase of ≥25% in PSA levels was indicative of progressive disease. Neither response nor progression was considered as stable disease. The Lu-177 PSMA-617 RLT led to a significant PSA response, with 50.6% of patients achieving a >50% decrease in PSA levels. Median overall survival (OS) and progression-free survival were 13.5 and 8.2 months, respectively. Patients receiving Lu-177 PSMA-617 RLT in combination with androgen receptor pathway inhibitors (ARPIs) had a higher OS compared to those receiving Lu-177 PSMA-617 RLT alone (18.2 vs 12.3 months, P = .265). The treatment was generally well-tolerated, with manageable side effects such as anemia and thrombocytopenia. This study provides real-world evidence supporting the effectiveness and safety of Lu-177 PSMA-617 RLT in mCRPC patients, particularly when used in combination with ARPIs. These findings contribute to the growing body of evidence on the potential benefits of PSMA-targeted therapies in advanced prostate cancer.

Incidental Meningioma With Altered PSMA Expression After Systemic Hormone Therapy and Local Radiotherapy Detected by 68 Ga-PSMA PET/CT.

ABSTRACT: A 59-year-old man underwent radical prostatectomy for adenocarcinoma in 2009. Because of the progression of PSA levels, a 68 Ga-PSMA PET/CT scan was performed in January 2020. A suspicious uptake was detected in the left cerebellar hemisphere, and there was no evidence of distant metastatic disease other than recurrent malignancy in the prostatectomy bed. MRI revealed a meningioma located in the left cerebellopontine angle. Although PSMA uptake of the lesion increased in the first imaging after hormone therapy, partial regression was noted after radiotherapy applied to this region.

COVID-19 Lung Findings Detected by 68Ga-PSMA PET/CT for Staging Purposes in Patients With Prostate Cancer.

ABSTRACT: We report 3 patients with COVID-19 findings in 68Ga-PSMA PET/CT taken for staging. The first patient, A 64-year-old man with prostate cancer, who had COVID-19 in November 2020 and whose treatment was completed, was observed to continue with COVID-19 findings in 68Ga-PSMA PET/CT in December 2020 before surgery. Other patients were asymptomatic for the disease. It was determined that a PSMA uptake in the lungs corresponding to the CT findings of COVID-19 had increased in 68Ga-PSMA PET/CT.

The Complex Genetic Landscape of Hereditary Ataxias in Turkey and Implications in Clinical Practice.

BACKGROUND: The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. OBJECTIVE: To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. METHODS: Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. RESULTS: Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. CONCLUSION: With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society.

18F-FDG PET/CT Findings of Non-Hodgkin Lymphoma Involving the Whole Genitourinary System

A sixty-two-year-old male patient underwent orchiectomy and was diagnosed with diffuse large B-cell lymphoma in the testicle and spermatic cord. 18F-FDG positron emission tomography/computed tomography (PET/CT) scanning was performed for initial staging. 18F-FDG PET/CT scan revealed multiple hyper-metabolic lymphadenopathies, lung lesions and mass lesions in the adrenal glands and kidneys. In addition, diffuse increased 18F-FDG uptake suggesting lymphomatous infiltration on the right testicle, prostate and left testicular veins were detected. The genitourinary system involvement is extremely rare in extranodal lymphomas and to the best of our knowledge this is the first case in the literature having 18F-FDG accumulating lesions in all genitourinary system structures.

Splenosis of the Liver Capsule.

Splenosis, a form of ectopic splenic tissue, is generally caused by heterotopic autotransplantation of splenic tissues after traumatic splenic rupture or splenectomy. The implants are often localized intraperitoneally, mostly in the left upper quadrant and splenic region. Hepatic foci are seen only on rare occasions. The differential diagnosis of splenosis foci from malignant masses can be challenging by conventional imaging and lead to unnecessary invasive procedures. This manuscript presents radiological and scintigraphic images of splenosis foci located in the peritoneal cavity and liver capsule of a 46-year-old man who underwent splenectomy due to traumatic splenic rupture 30 years ago.

Contribution of 18F-FDG PET/CT to Staging of Head and Neck Malignancies.

OBJECTIVES: Accurate staging of head and neck cancer (HNC) plays an important role in patient management as well as protection of functional characteristics of the head and neck region. Our aim was to investigate the contribution of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) as part of HNC staging to clinical evaluation and treatment planning. METHODS: Clinical records of 138 HNC cases who has undergone 18F-FDG PET/CT imaging were retrospectively reviewed. Sixty-five cases who had accessible clinical follow-up data were included in the study group, and their PET/CT and conventional imaging findings were evaluated. RESULTS: In the case group with a PET/CT and magnetic resonance imaging (MRI) for evaluation of primary lesion the sensitivity rates for PET/CT and MRI were calculated as 91.3% and 82.6%, the positive predictive values (PPV) as 91.3% and 82.6%, specificity as 71.4% and 42.8%, and the negative predictive value (NPV) as 71.4% and 42.8%, respectively. In terms of metastatic lymph node evaluation, the sensitivity was calculated as 100% and 88.8%, the NPV as 100% and 83.3%, respectively. The PPV and specificity was 100% for both modalities. In the case group with CT for primary lesion evaluation, the sensitivity and PPV were found as 95.2% and 100% for PET/CT, and as 85.7% and 94.7% for CT, respectively. in metastatic lymph node evaluation, the sensitivity was found as 100% for PET/CT and 50% for CT, and the PPV, specificity and NPV were determined as 100% for both methods. PET/CT findings resulted in a change in 'tumor, node, metastasis' staging in 5 cases. CONCLUSIONS: PET/CT in HNC contributes to staging, thus playing a role in treatment planning, especially in patients with locally advanced disease.

Evaluation of bone mineral density and related parameters in patients with haemophilia: a single center cross-sectional study.

Haemophilia has been associated with low bone mineral density (BMD) probably due to some predisposing factors. The aim of this study was to evaluate the relationship between BMD and potential clinical predictors in adult haemophilic patients. Fortynine patients with moderate and severe haemophilia were enrolled. BMD was measured by Dual Energy X-Ray Absorptiometry (DXA) and blood tests were performed for vitamin D, calcium, phosphore, alkaline phosphatase and parathormone levels. Functional Independence Score in Haemophilia (FISH) and Haemophilia Joint Health Score (HJHS) were used to assess musculoskeletal functions. Body mass index (BMI), Hepatitis C virus (HCV)/Human immunodeficiency virus (HIV) seropositivity and smoking status were also recorded. BMD was found lower than expected for reference age in 34.8% of patients of less than 50 years old. In patients older than 50 years, 66.6% of them had osteoporosis and 33.3% of them had normal BMD. FISH score was statistically significant correlated with BMD of total hip (TH) and femur neck (FN) but not with lumbar spine (LS). In eligible patients, there was also a statistically significant correlation between BMD of TH and HJHS. Vitamine D deficiency was common and found in 77.5% of patients, although there was no significant correlation with BMD. Also no correlation was found between BMD and blood tests, HCV/HIV status, BMI and smoking. This study confirmed that patients with haemophilia have an increased prevelance of low BMD even in younger group. Our results showed that there are significant correlations between FISH score and BMD of TH and FN and also between HJHS score and BMD of TH. Thus, using scoring systems may be beneficial as a simple predictors of BMD to reflect the severity of haemophilic arthropathy.

Blood RNA biomarkers in prodromal PARK4 and rapid eye movement sleep behavior disorder show role of complexin 1 loss for risk of Parkinson's disease.

Parkinson's disease (PD) is a frequent neurodegenerative process in old age. Accumulation and aggregation of the lipid-binding SNARE complex component α-synuclein (SNCA) underlies this vulnerability and defines stages of disease progression. Determinants of SNCA levels and mechanisms of SNCA neurotoxicity have been intensely investigated. In view of the physiological roles of SNCA in blood to modulate vesicle release, we studied blood samples from a new large pedigree with SNCA gene duplication (PARK4 mutation) to identify effects of SNCA gain of function as potential disease biomarkers. Downregulation of complexin 1 (CPLX1) mRNA was correlated with genotype, but the expression of other Parkinson's disease genes was not. In global RNA-seq profiling of blood from presymptomatic PARK4 indviduals, bioinformatics detected significant upregulations for platelet activation, hemostasis, lipoproteins, endocytosis, lysosome, cytokine, Toll-like receptor signaling and extracellular pathways. In PARK4 platelets, stimulus-triggered degranulation was impaired. Strong SPP1, GZMH and PLTP mRNA upregulations were validated in PARK4. When analysing individuals with rapid eye movement sleep behavior disorder, the most specific known prodromal stage of general PD, only blood CPLX1 levels were altered. Validation experiments confirmed an inverse mutual regulation of SNCA and CPLX1 mRNA levels. In the 3'-UTR of the CPLX1 gene we identified a single nucleotide polymorphism that is significantly associated with PD risk. In summary, our data define CPLX1 as a PD risk factor and provide functional insights into the role and regulation of blood SNCA levels. The new blood biomarkers of PARK4 in this Turkish family might become useful for PD prediction.

Recurrence Incidence in Differentiated Thyroid Cancers and the Importance of Diagnostic Iodine-131 Scintigraphy in Clinical Follow-up.

OBJECTIVE: Differentiated thyroid cancers (DTC) are tumors with good prognosis. However, local recurrence or distant metastasis can be observed. In our study, we aimed to investigate the incidence of recurrence and the importance of diagnostic iodine-131 whole body scan (WBS) in clinical follow-up in patients with DTC. METHODS: The clinical data of 217 patients with DTC who were followed-up more than 3 years were reviewed retrospectively. The incidence of recurrence was investigated in a group of patients who had radioactive iodine (RAI) treatment and showed no sign of residual thyroid tissue or metastasis with diagnostic WBS that was performed at 6-12 months after therapy and had a thyroglobulin (Tg) level lower than 2 ng/dl. RESULTS: At the time of diagnosis, ten cases had thyroid capsule invasion, 25 cases had extra-thyroid soft tissue invasion, 11 patients showed lymph node metastasis and four patients had distant organ metastasis. One hundred forty-five patients had RAI treatment at ablation dose (75-100 mCi), whereas 35 patients had RAI treatment at metastasis dose (150-200 mCi). Thirty-seven patients with papillary microcarcinoma did not receive RAI treatment. In 12 (%7.5) of the 160 patients who were considered as "successful ablation", a recurrence was identified. Recurrence was detected by diagnostic WBS in all cases and stimulated Tg level was <2 ng/dL with the exception of the two cases who had distant metastasis. CONCLUSION: Identification of pathological findings with WBS in patients who developed local recurrence in the absence of elevated Tg highlights the importance of diagnostic WBS in clinical follow-up.

False-Positive 131I Uptake in a Benign Bone Lesion on Post-therapy Scan.

A 56-year-old woman underwent near-total thyroidectomy and papillary thyroid carcinoma without extrathyroidal extension was diagnosed. The serum thyroglobulin (Tg) level was 2.4 µg/L, and anti-Tg was negative when serum thyroid-stimulating hormone level was 85 µIU/mL. She received 100 mCi (3.7 GBq) of 131I. Besides the residual thyroid tissue, a focal uptake in the left clavicular bone was seen on posttherapy 131I images. Then, CT and MRI were performed to diagnosis. All imaging findings suggested that it was a benign bone cyst. At 6-month follow-up, the serum Tg level was undetectable with the thyroid-stimulating hormone level of more than 150 µIU/mL.

18F-FDG and 18F-NaF PET/CT Findings of a Multiple Myeloma Patient With Thyroid Cartilage Involvement.

Thyroid cartilage is a very rare extramedullary involvement location in multiple myeloma. We present both F-NaF and F-FDG PET/CT findings of a multiple myeloma patient with thyroid cartilage involvement. In this patient, increased FDG and more intensely increased NaF uptake were seen on thyroid cartilage. In addition, some bone lesions had more intense NaF than FDG uptake, and some were only NaF avid. Although F-FDG PET/CT has an important role in plasma cell neoplasms, we considered that F-NaF PET/CT is also very useful to detect small lytic lesions that might be overlooked on F-FDG PET/CT.

The distinct genetic pattern of ALS in Turkey and novel mutations.

The frequency of amyotrophic lateral sclerosis (ALS) mutations has been extensively investigated in several populations; however, a systematic analysis in Turkish cases has not been reported so far. In this study, we screened 477 ALS patients for mutations, including 116 familial ALS patients from 82 families and 361 sporadic ALS (sALS) cases. Patients were genotyped for C9orf72 (18.3%), SOD1 (12.2%), FUS (5%), TARDBP (3.7%), and UBQLN2 (2.4%) gene mutations, which together account for approximately 40% of familial ALS in Turkey. No SOD1 mutations were detected in sALS patients; however, C9orf72 (3.1%) and UBQLN2 (0.6%) explained 3.7% of sALS in the population. Exome sequencing revealed mutations in OPTN, SPG11, DJ1, PLEKHG5, SYNE1, TRPM7, and SQSTM1 genes, many of them novel. The spectrum of mutations reflect both the distinct genetic background and the heterogeneous nature of the Turkish ALS population.

Radioiodine uptake in an ovarian mature teratoma detected with SPECT/CT.

A 28-year-old woman underwent a near-total thyroidectomy for papillary carcinoma. Before radioiodine therapy, the serum thyroid-stimulating hormone level was 50 µIU/mL, the thyroglobulin level was 1 µg/L, and the antithyroglobulin was negative. She received 100 mCi of I for ablation of residual thyroid tissue. After therapy, I whole-body scan demonstrated focal uptake in the right pelvic area, which localized to the right ovary on SPECT/CT fusion images. The ovarian cyst was resected, and histopathological examination revealed a mature teratoma without thyroid tissue component. At 6-month follow-up, the whole-body radioiodine scan was normal, and serum thyroglobulin was undetectable.

12q24 locus association with type 1 diabetes: SH2B3 or ATXN2?

Genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the genes SH2B3 and ATXN2 in its core, to be associated with an exceptionally wide spectrum of disease susceptibilities. Hematopoietic traits of red and white blood cells (like erythrocytosis and myeloproliferative disease), autoimmune disorders (like type 1 diabetes, coeliac disease, juvenile idiopathic arthritis, rheumatoid arthritis, thrombotic antiphospholipid syndrome, lupus erythematosus, multiple sclerosis, hypothyroidism and vitiligo), also vascular pathology (like kidney glomerular filtration rate deficits, serum urate levels, plasma beta-2-microglobulin levels, retinal microcirculation problems, diastolic and systolic blood pressure and hypertension, cardiovascular infarction), furthermore obesity, neurodegenerative conditions (like the polyglutamine-expansion disorder spinocerebellar ataxia type 2, Parkinson's disease, the motor-neuron disease amyotrophic lateral sclerosis, and progressive supranuclear palsy), and finally longevity were reported. Now it is important to clarify, in which ways the loss or gain of function of the locally encoded proteins SH2B3/LNK and ataxin-2, respectively, contribute to these polygenic health problems. SH2B3/LNK is known to repress the JAK2/ABL1 dependent proliferation of white blood cells. Its null mutations in human and mouse are triggers of autoimmune traits and leukemia (acute lymphoblastic leukemia or chronic myeloid leukemia-like), while missense mutations were found in erythrocytosis-1 patients. Ataxin-2 is known to act on RNA-processing and trophic receptor internalization. While its polyglutamine-expansion mediated gain-of-function causes neuronal atrophy in human and mouse, its deletion leads to obesity and insulin resistance in mice. Thus, it is conceivable that the polygenic pathogenesis of type 1 diabetes is enhanced by an SH2B3-dysregulation-mediated predisposition to autoimmune diseases that conspires with an ATXN2-deficiency-mediated predisposition to lipid and glucose metabolism pathology.

Comparison of gated myocardial perfusion SPECT, echocardiography and equilibrium radionuclide ventriculography in the evaluation of left ventricle contractility.

OBJECTIVES: In this study, we investigated the reliability of gated myocardial perfusion single-photon emission computerized tomography (GSPECT) for the evaluation of left ventricle (LV) function. We compared left ventricle ejection fraction (LVEF) calculated with GSPECT with the values derived from planar equilibrium-gated radionuclide ventriculography (ERVG) and echocardiography (ECHO). STUDY DESIGN: Forty-eight patients with suspected coronary artery disease (CAD), who were referred for evaluation of myocardial perfusion and LV function and underwent two-day 99mTc-MIBI protocol GSPECT and ERVG, were examined retrospectively. LVEF was calculated with GSPECT Myometrix software, and wall motion and thickness were calculated with QGS analysis program. In the ERVG study, LVEF values were calculated using left anterior oblique images. In the GSPECT and ERVG study, wall motion was evaluated visually and scored. LVEF values and wall motion data measured with ECHO were noted. RESULTS: For all cases, there was a significant correlation between LVEF values calculated by GSPECT and ERVG. Numerical LVEF values of 30 patients measured with ECHO showed no significant difference from the values measured with GSPECT. When 240 segments obtained from 48 patients were examined, the correlation between GSPECT and ERVG was 77.5% and between GSPECT and ECHO was 75.4% by visual wall motion analysis. Quantitatively calculated wall motion and thickness scores of segments visually defined as normokinetic were significantly higher than segments visually defined as having contraction defect. CONCLUSION: GSPECT can be used safely in clinical practice for the evaluation of LV function. Quantitatively calculated wall motion and thickness scores are promising methods to verify the visual evaluation.

Scintigraphic methods to evaluate alterations of gastric and esophageal functions in female obesity.

OBJECTIVE: Altered gastrointestinal function has frequently been observed in obese patients. The aim of this study was to investigate the frequency of gastro-esophageal reflux (GER) and to determine the alterations of gastric emptying and esophageal transit by scintigraphic methods in obese patients. METHODS: Scintigraphic studies of 50 obese female non-diabetic patients who had not received any treatment for weight control were retrospectively reviewed. Mean Body Mass Index (BMI) was 34.96±3.04 kg/m(2) (range:32-39 kg/m(2)). All subjects were submitted to scintigraphic evaluation of esophageal transit, gastro-esophageal reflux, gastric emptying and presence of Helicobacter pylori infection. The data of obese patients were compared with those of sex-age matched 30 non-obese cases who were selected from our clinical archive. RESULTS: In obese group, seventeen (34%) patients were found to be GER positive scintigraphically; mean gastric emptying time (t½) was 59.18±30.8 min and the mean esophageal transit time was 8.9±7.2 s. Frequency of positive GER scintigraphy and the mean value of esophageal transit time were significantly higher in obese patients than non-obese control subjects. Gastric emptying time and esophageal transit time values were significantly longer in GER positive obese patients than GER negative ones. There was no statistically significant difference in the frequency of positive C14 urea breath test between obese and non-obese subjects and there were also no statistically significant correlations between BMI, GER, esophageal transit time and gastric emptying time. CONCLUSION: In our study, 42 of the 50 obese patients had esophago-gastric motility alterations. The significance of these alterations in obesity is not fully understood, but it is believed that these changes could be because of potential contributing factors in the development or maintenance of obesity or changes in eating habits. CONFLICT OF INTEREST: None declared.

Fluorine-18 fluorodeoxyglucose PET-CT for extranodal staging of non-Hodgkin and Hodgkin lymphoma.

PURPOSE: We aimed to evaluate the role of fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) involving care-dose unenhanced CT to detect extranodal involvement in patients with non-Hodgkin and Hodgkin lymphoma. MATERIALS AND METHODS: Lymphoma patients (35 Hodgkin lymphoma, 75 non-Hodgkin lymphoma) who were referred for 18F-FDG PET-CT imaging, following a diagnostic contrast-enhanced CT (CE-CT) performed within the last month, were included in our study. A total of 129 PET-CT images, and all radiologic, clinical, and pathological records of these patients were retrospectively reviewed. RESULTS: In total, 137 hypermetabolic extranodal infiltration sites were detected by 18F-FDG PET-CT in 62 of 110 patients. There were no positive findings by CE-CT that reflected organ involvement in 40 of 137 18F-FDG-positive sites. The κ statistics revealed fair agreement between PET-CT and CE-CT for the detection of extranodal involvement (κ=0.60). The organs showing a disagreement between the two modalities were the spleen, bone marrow, bone, and thyroid and prostate glands. In all lesions that were negative at CE-CT, there was a diffuse 18F-FDG uptake pattern in the PET-CT images. The frequency of extranodal involvement was 51% and 58% in Hodgkin and non-Hodgkin lymphoma patients, respectively. There was a high positive correlation between the maximum standardized uptake values of the highest 18F-FDG-accumulating lymph nodes and extranodal sites (r=0.67) in patients with nodal and extranodal involvement. CONCLUSION: 18F-FDG PET-CT is a more effective technique than CE-CT for the evaluation of extranodal involvement in Hodgkin and non-Hodgkin lymphoma patients. PET-CT has a significant advantage for the diagnosis of diffusely infiltrating organs without mass lesions or contrast enhancement compared to CE-CT.

An update on molecular biology of thyroid cancers.

Differentiated thyroid cancer (DTC) is the most common endocrinological malignancy. There are several histological variants such as papillary and follicular thyroid carcinoma. Many patients with well-differentiated subtypes of DTC are cured by surgery alone or with radioiodine, while poorly differentiated types usually have a worse prognosis. The aggressiveness of thyroid tumors is closely linked to specific gene alterations. Several diagnostic and prognostic molecular markers such as BRAF and RAS point mutations; RET/PTC and PAX8/PPARγ gene rearrangements; MAPK, PI3K, p53, Wnt-beta catenin, HIF1α and NF-kappaB signaling pathways; microRNA profiles and aberrant methylation have been demonstrated in more than 70% of DTC. Diagnostic use of these molecular markers may be optimized for identifying higher risks of mortality, tumor recurrence and metastatic potential. Understanding the molecular biology of thyroid cancers can be an important avenue for diagnosis and treatment of radioiodine-refractory or inoperable DTC patients with novel molecular targeted therapeutic agents.

Genome-wide copy number variation in sporadic amyotrophic lateral sclerosis in the Turkish population: deletion of EPHA3 is a possible protective factor.

The genome-wide presence of copy number variations (CNVs), which was shown to affect the expression and function of genes, has been recently suggested to confer risk for various human disorders, including Amyotrophic Lateral Sclerosis (ALS). We have performed a genome-wide CNV analysis using PennCNV tool and 733K GWAS data of 117 Turkish ALS patients and 109 matched healthy controls. Case-control association analyses have implicated the presence of both common (>5%) and rare (<5%) CNVs in the Turkish population. In the framework of this study, we identified several common and rare loci that may have an impact on ALS pathogenesis. None of the CNVs associated has been implicated in ALS before, but some have been reported in different types of cancers and autism. The most significant associations were shown for 41 kb and 15 kb intergenic heterozygous deletions (Chr11: 50,545,009-50,586,426 and Chr19: 20,860,930-20,875,787) both contributing to increased risk for ALS. CNVs in coding regions of the MAP4K3, HLA-B, EPHA3 and DPYD genes were detected however, after validation by Log R Ratio (LRR) values and TaqMan CNV genotyping, only EPHA3 deletion remained as a potential protective factor for ALS (p = 0.0065024). Based on the knowledge that EPHA4 has been previously shown to rescue SOD1 transgenic mice from ALS phenotype and prolongs survival, EPHA3 may be a promising candidate for therepuetic interventions.