OBJECTIVE:Approximately 5-10% of the cases with colorectal cancers have a hereditary cancer syndrome. MUTYH is a DNA base excision repair gene, and its mutation can induce the development of polyposis and colorectal cancer. Additionally, MUTYH repair gene may interact with the DNA mismatch repair system. The aim of this study was to investigate the clinicopathological features of colorectal cancer cases carrying germline MUTYH mutations. METHODS:Among patients genetically tested using large hereditary cancer panels, data of those carrying germline MUTYH mutations were retrieved from the archive files. Then, the patients who had colorectal cancer were included in the study. RESULTS:Ten male and three female colorectal cancer patients with pathogenic (n=10) and variant of uncertain significance MUTYH mutations (n=3) were included in the study. While seven cases had homozygous MUTYH mutations, six patients carried heterozygous MUTYH mutations. The patients had c.800C>T p.P267L (n=4), c.1353_1355delGGA p.E452del (n=4), c.1087C>T p.Q363 (n=1), c.631G>A p.V211I (n=1), c.180A>G p.R60R (n=1), c.509G>A p.G170E (n=1) and c.650G>A p.R217H (n=1) mutations. The ascending colon was the most common site of involvement. Six cases with homozygous and one case with double heterozygous mutations had polyposis. Cases with homozygous (n=1) and heterozygous (n=1) MUTYH mutations were found to be MSH2-deficient. In both MSH2-deficient cases, the tumors were located in the ascending colon, and the case with a homozygous mutation had >100 polyps. CONCLUSION:Given that the MUTYH mutation is rarely seen in cases of colorectal cancers, we believe that our findings may contribute to identifying potential clinical and therapeutic implications for individuals with this mutation.

Objective Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing syndrome. Recent evidence, particularly the 2023 European Society of Endocrinology guidelines, clinically classifies cortisol excess into overt Cushing syndrome and mild autonomous cortisol secretion. Germline mutations in the Armadillo repeat-containing 5 (ARMC5) gene have been identified in 20%–55% of patients with PBMAH. This study aimed to describe the clinical, radiological, and biochemical characteristics of PBMAH; classify cortisol secretion according to updated guidelines; and evaluate surgical and conservative treatment outcomes. Methods This retrospective cohort study included 58 patients with bilateral adrenal macronodules who underwent ARMC5 genetic testing at a tertiary center between 2023 and 2025. Clinical, imaging, laboratory, and genetic data were collected. Mild autonomous cortisol secretion was defined according to the 2023 European guidelines as a post–dexamethasone suppression test cortisol level >1.8 μg/dL in the absence of overt Cushing syndrome features. Postoperative and follow-up data, including hormonal assessments and remission criteria, were recorded. Results A total of 58 patients were included; 14 (23.7%) were male, and the mean age was 57.7 years (39–73). Four patients (6.9%) with overt Cushing syndrome carried germline ARMC5 mutations, three of whom belonged to the same family, supporting an autosomal dominant pattern of inheritance. Among them, 34 patients with mild autonomous cortisol secretion and 20 patients with nonfunctional PBMAH were managed conservatively. Unilateral laparoscopic adrenalectomy was performed in five patients, all of whom achieved biochemical and clinical remission during follow-up (median, 14 months). No postoperative adrenal insufficiency or persistent hypercortisolism was observed. Conclusion PBMAH demonstrates a broad clinical spectrum, ranging from nonfunctional disease to overt Cushing syndrome. The updated classification of cortisol secretion (mild autonomous cortisol secretion vs. overt Cushing syndrome) improves clinical stratification and supports treatment decision-making. ARMC5 genetic analysis contributes to diagnostic confirmation, facilitates cascade family screening, and enables identification of asymptomatic carriers. Unilateral adrenalectomy is effective in patients with overt Cushing syndrome, whereas surveillance is appropriate for those with mild autonomous cortisol secretion or nonfunctional PBMAH.

Background/Objectives: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms may influence folate metabolism and DNA synthesis, potentially affecting disease characteristics and clinical outcomes in hematologic malignancies. This study investigated the associations of MTHFR C677T and A1298C polymorphisms with clinical features and survival outcomes in adult patients with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). Methods: A total of 92 adult patients with ALL or NHL treated with standard chemotherapy were retrospectively analyzed. MTHFR C677T and A1298C genotypes were determined using real-time polymerase chain reaction. Associations between genotypes and baseline clinical features, treatment response, toxicity, overall survival (OS), and progression-free survival (PFS) were examined. Results: The C677T heterozygous genotype was significantly associated with the presence of B symptoms (p = 0.027). No significant differences were observed across genotypes with respect to other baseline clinical features, treatment response, or treatment-related toxicity. In the overall cohort (ALL + NHL), OS and PFS did not differ significantly by C677T or A1298C genotypes. However, in the NHL cohort, carriers of the C677T variant demonstrated significantly shorter PFS (p = 0.048) and a non-significant trend toward lower OS. This association was also observed in the DLBCL subgroup for PFS (p = 0.043), with a similar non-significant trend observed for OS. Conclusions: Although MTHFR genotyping appears to have limited value for broad clinical stratification, the observed association between the C677T polymorphism and PFS in NHL-particularly in the DLBCL subgroup-suggests a potential subtype-specific relevance that warrants further validation in larger, disease-specific cohorts.

This study aimed to identify disease-related genetic variants in 41 patients with retinitis pigmentosa (RP) and to evaluate their phenotypic effects on the retina and choroid. Patients diagnosed with RP underwent targeted next-generation sequencing of RP-related genes and mitochondrial DNA analysis, with genetic counseling. Variants were classified according to ACMG guidelines. Central macular thickness (CMT), retinal nerve fiber layer thickness (RNFLT), subfoveal choroidal thickness (SfCT), foveal avascular zone area (FAZa), ellipsoid zone (EZ) integrity, and vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) were assessed using OCT and OCTA. Patients were classified into three groups: Group 1 (USH2A; n = 11), Group 2 (other single-gene variants; n = 21), and Group 3 (multiple-gene variants; n = 9). There were no significant differences in age, sex, consanguinity, symptom onset, disease duration, best-corrected visual acuity, intraocular pressure, RNFLT, or EZ integrity. Pairwise comparisons showed a higher preserved EZ rate in Group 2 (66.7

Proprotein convertase 1/3 (PC1/3), encoded by PCSK1, is expressed in neuronal and endocrine cell types, where it activates a number of protein precursors that play roles in energy homeostasis. Biallelic PCSK1 loss-of-function mutations cause a polyendocrinopathy; a total of 34 patients were reported. An infant with congenital malabsorptive diarrhea of all carbohydrates underwent exome sequencing (ES), with particular consideration of PC1/3 deficiency, but no mutations were found. The onset of obesity in the second year of life increased suspicion of PC1/3 deficiency in the proband, as well as in his equally affected cousin. Transcript analysis revealed minor amounts of an aberrant PCSK1 transcript containing intron 9 sequence and encoding a premature stop codon (p.Pro400Valfs*35). A deep intronic PCSK1 variant, NG_021161.1(NM_000439.5):c.1196+2681T>A, was found to segregate in the proband's family with the disease. A minigene approach demonstrated that the identified deep-intronic variant underlies pseudo-exon inclusion of the intron 9 sequence in the transcript. The characteristic phenotype of PC1/3 deficiency might require extended genetic testing to make a timely diagnosis.

Autosomal dominant sensorineural hearing loss (ADSNHL) is a genetically heterogeneous disorder caused by pathogenic variants in various genes, including MYH14. However, the interpretation of pathogenicity for MYH14 variants remains a challenge due to incomplete penetrance and the lack of functional studies and large families. In this study, we performed exome sequencing in six unrelated families with ADSNHL and identified five MYH14 variants, including three novel variants. Two of the novel variants, c.571G > C (p.Asp191His) and c.571G > A (p.Asp191Asn), were classified as likely pathogenic using ACMG and Hearing Loss Expert panel guidelines. In silico modeling demonstrated that these variants, along with p.Gly1794Arg, can alter protein stability and interactions among neighboring molecules. Our findings suggest that MYH14 causative variants may be more contributory and emphasize the importance of considering this gene in patients with nonsyndromic mainly post-lingual severe form of hearing loss. However, further functional studies are needed to confirm the pathogenicity of these variants.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract Introduction Obesity is a known condition when the energy taken is more than the energy consumed. According to the World Obesity Atlas data, 1 out of every five women and 1 out of every seven men will live with obesity by 2030.The prevalence of obesity was 21.1% in Turkey (2019). Although environmental factors and changes in dietary patterns are essential in this increase, genetic factors also have an effect. Mutations in genes that affect catecholamine function, which play an essential role in energy consumption and lipolysis, also lead to obesity. One of these critical genes is the β2-adrenergic receptor gene (ADRB2). It was previously reported that it is responsible for regulating lipolysis and thermogenesis and is mainly expressed in the adipose tissues. This gene induces catecholamine activation and leads to lipid mobilization in adipose tissue. Clinical Case A 25-year-old male patient applied to our outpatient clinic with obesity, sexual dysfunction. The patient had been overweight since childhood and did not use any medication at admission. On physical examination, his body mass index:50.8 kg/cm2.and has only hair on the genital area and axilla. His parents are consanguineous, and his mother, father, and brother are also obese. He had diabetes mellitus, hypolipidemia, hypogonadotropic hypogonadism, and GH deficiency in his initial tests (Table-1). The other pituitary hormones were usual. There was not any pathology in the pituitary and brain magnetic resonance images. LHRH test result was interpreted as hypothalamic dysfunction. The insulin hypoglycemia test was performed due to growth hormone deficiency to accurate to GH deficiency. Clinic exome sequencing was performed on the patient, and a de novo heterozygous mutation in the ADRB2 gene was detected, which has a role in lipolysis, and thermogenesis and hence is important for obesity. Two more mutations were identified that related to thyroid functions. The DUOX2 gene variant has an association with thyroid dyshormonogenesis, and the IRS4 gene variant has a role in hypothyroidism. Further studies are needed to identify the pathogenicity of variants. Molecular identification of mutations has important implications for personalized medicine, including genetic counseling and the development of specific treatment protocols. We started the patient with exenatide 10 mg/day, metformin 2000 mg/day, testosterone propionate, and a diet program. Conclusion Studies show that low ADRB2 expression increases the risk of obesity. Obesity is increasing rapidly over time globally, and it is necessary to know the underlying pathophysiologies and genetic etiologies and to develop new treatment algorithms for this in order to reduce mortality and morbidity. Therefore, gene mutations underlying obesity, the metabolic changes it causes, environmental factors, and diet should be considered. Considering the scarcity of available anti-obesity drugs, understanding the genetic makeup may be influential in developing new therapeutic targets.

Limb-girdle muscular dystrophies (LGMDs) are a heterogenous group of genetic diseases generally characterized by proximal muscle weakness (1).Among them, LGMD-R18 is an autosomal recessive form caused by a mutation on the 4q35 locus of the gene encoding transport protein particle complex 11 (TRAPPC11).The available clinical data is limited to case reports and series of Syrian, Hispanic, Chinese, and Turkish origin (1,2,3,4,5,6).Our aim was to contribute to the existing data by presenting a LGMD-R18 case, to the best of our knowledge, the first reported from Türkiye.A 25-year-old, consanguineous male patient visited our clinic due to difficulty in walking and frequent falls.He began to walk at a normal age, but suffered a developmental delay following a single non-febrile epileptic seizure at age three.While his seizures did not recur, he started to fall behind his peers in terms of physical and intellectual development, and from the age of eight, had difficulty in climbing stairs and experienced frequent falls.He was the third of four siblings, but neither his siblings nor his parents reported similar complaints.His muscle strength was 4/5 in the bilateral forearm flexors and extensors and the wrist extensors, 4/5 in the neck flexors, 3/5 in the neck extensors, 2/5 in the hip flexors, 2/5 in the hip extensors, 2/5 in the thigh adductors, and +4/5 in the knee flexors and extensors.His deep tendon reflexes were normal and his Gower's sign was positive.

Objective: The aim of this study was to determine the frequency of germline variants in BRCA1, BRCA2, CDH1, PALB2, PTEN and TP53 in patients admitted to a medical genetics clinic with breast cancer and to assess these identified variants according to published genetic, surgical and oncological perspectives.Materials and Methods: Medical history, and cancer diagnosis information for 195 independent probands with operated breast cancer were collected from requisition forms and medical records. The exonic regions and exon-intron junctions in BRCA1, BRCA2, CDH1, PALB2, PTEN and TP53 genes were sequenced. Analysis of fastq files was performed on the Qiagen Clinical Insight-Analyse Universal with panel-specific pipeline and vcf files were interpreted clinically using Qiagen Clinical Insight-Interpret.Results: Gene variants (pathogenic, likely pathogenic and variants of unknown significance) were detected in 53 (27.2%). Detailed information about the patients (age of diagnosis, family history, gender), cancer stage, tumour characteristics (ER, PR, human epidermal growth factor receptor 2 status) and all information related to the detected variants (gene, location, nucleotide and amino acid change, exon number, impact, mutation classification, dbSNP number and HGMD variant class) were assessed. In total, 58 mutations were identified including 14 novel, previously unreported variants.Conclusion: Molecular characterization and identification of mutations have important implications for predictive, preventive, and personalized medicine, including genetic counseling and development of specific treatment protocols. We emphasize variants of unknown significance (VUS) as the clinical significance of VUS changes over time and variant classification is important for clinical molecular genetic testing and clinical guidance. This study may provide new insights into risk assessment for variants in CDH1, PALB2, PTEN and TP53, in addition to BRCA1 and BRCA2, which may prove useful for clinical management of breast cancer patients. Further studies are needed to identify the common gene variants in the Turkish population and evaluate the pathogenity of VUS.

Background: Hereditary Hemochromatosis (HH) is an inherited iron metabolism disorder characterized by excessive iron accumulation in the liver, heart, pancreas and other endocrine organs. Although it is often associated with mutations in the HFE gene, it can also be caused by mutations associated with HJV, TFR-2 and ferroportin. JAK2 V617F (+) Polycythemia Vera (PV) is the most common cause of acquired primary erythrocytosis and has been reported very rarely in patients with HH. Aims: We presented two polycythemia vera patients with a diagnosis of concomitant hereditary hemochromatosis. Methods: Presence of HFE gene mutation and jak-2 V617F mutation was determined by PCR test Results: Case 1: N.G, a 67-year-old male patient with a history of hypertension, insulin-dependent diabetes mellitus and cerebrovascular accident was diagnosed with PV in another center in 2007. The patient was JAK2 V617F (+) and the tests performed in our laboratory after phlebotomies were EPO: 7.8 mIU/ml, ferritin: 34 ng/dl, transferrin saturation: 49%. Bone marrow aspiration biopsy revealed hypercellularity with erythroid and megakaryocytic hyperplasia. Although Hb/Hct levels were within the targeted range with hydroxyurea 500 mg 2x1 treatment, he was followed up with frequent phlebotomies due to persistent pruritus. After phlebotomy, there was a significant improvement in his pruritus. He was using clopidogrel as antiaggregant treatment. During follow-up, there was deterioration in blood glucose regulation and an increase in insulin requirement. In June 2018, he developed widespread hyperpigmentation on his skin. Due to unregulated diabetes, hyperpigmentation, and high ferritin levels despite frequent phlebotomy, he was examined for HH. He was found to be heterozygous positive for the HFE gene H63D mutation. The patient is still being followed up with HU 2X1 and phlebotomy without any problem. Case 2: E.H, a 57-year-old male patient with a history of hypertension and type 2 diabetes mellitus was diagnosed with PV in 2015. He was JAK2 V617F(+) and at diagnosis EPO:3.7 mIU/ml, ferritin:1403 ng/ml, transferrin saturation:63%. Bone marrow aspiration biopsy revealed hypercellularity and erythroid hyperplasia. Since he was a low-risk patient under the age of 60 and had no history of thrombosis, he was followed up with ASA 100 mg/day and intermittent phlebotomies. Similar to the first case, persistent pruritus was present despite the normal Hb/Hct level. Since hyperferritinemia was not expected in polycythemia vera and the patient was diabetic, he was examined for HH. In the HFE gene analysis, the H63D mutation was found to be heterozygous. Due to the frequent need for phlebotomy, the patient is considered to start treatment with hydroxyurea, and the follow-up still continues. Summary/Conclusion: The association of HH and PV has been rarely reported in the literature, and its clinical significance is not clearly known. In the presence of unexplained high ferritin levels in PV, even if the clinical findings are unclear, screening for HH may be recommended as an appropriate approach. The role of HFE genotypes in the development of myeloproliferative diseases is unknown. Clinical data accumulation is needed to elucidate iron metabolism and prognostic features in PV patients with HFE mutations. Keywords: polycythemia vera, hereditary hemochromatosis, JAK2 V617F, HFE mutation

Kültür, insan topluluklarının yaşadıkları dünyada uzun zaman diliminde doğruluğunu veya yanlışlığını denetleyerek karar verdikleri, ortak bilinçle kabullendikleri ve benimseyerek nesilden nesle aktardıkları değerler bütünüdür. Kültürel belleğin önemli bir bölümünü oluşturan somut olmayan kültürel miras unsurlarını koruma amacıyla hazırlanan ve Türkiye Cumhuriyeti’nin 2006’da taraf olduğu UNESCO Somut Olmayan Kültürel Mirasın Korunması Sözleşmesi, SOKÜM unsurlarını yaşatarak koruma prensibine dayanmaktadır. 2014’te UNESCO İnsanlığın Somut Olmayan Kültürel Mirası Temsili Listesi’ne Türk kâğıt süsleme sanatı olarak kaydedilmiş olan ebru sanatı, kadim zamanlardan bugüne Türklerin yaşayan kültürel miras unsurlarından biridir. Bu araştırmada ebru sanatının kültürel miras olarak aktarılarak yaşatılmasında medyanın etkisi olduğu varsayımı, ortaokul düzeyinde belirlenen örneklem üzerinde denetlenmiştir. Çalışmanın amacı, ebru sanatının ortaokul öğrencilerindeki farkındalık durumunda medyanın etkisini tespit etmektir. Araştırmada öncelikle detaylı bir literatür taraması yapılarak elde edilen kaynaklar nitel bir yöntem olan doküman analizi ile incelenmiştir. Nicel araştırma yönteminden de yararlanılan çalışmada veri toplama aracı olarak on beş sorudan oluşan anket formu kullanılmıştır. Veriler; Excel, Google Form, Jamovi program ve uygulamalarıyla “oranlama”, “yüzde”, “aritmetik ortalama”, “betimsel analiz” teknikleriyle incelenmiş; öğrencilerin sınıf düzeyleri, cinsiyet oranlarına göre karşılaştırmalı olarak analiz edilmiştir. Araştırma sonunda somut olmayan kültürel mirasın korunması ve aktarılmasında okullar önemini muhafaza etmekle birlikte medyanın -özellikle video paylaşım platformları ve sosyal medyakültür aktarımı açısından önemli yer edindiği tespit edilmiştir.