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Insufficient dietary folate intake, hereditary malabsorption, or defects in folate transport may lead to combined immunodeficiency (CID). Although loss of function mutations in the major intestinal folate transporter PCFT/SLC46A1 was shown to be associated with CID, the evidence for pathogenic variants of RFC/SLC19A1 resulting in immunodeficiency was lacking. We report two cousins carrying a homozygous pathogenic variant c.1042 G > A, resulting in p.G348R substitution who showed symptoms of immunodeficiency associated with defects of folate transport. SLC19A1 expression by peripheral blood mononuclear cells (PBMC) was quantified by real-time qPCR and immunostaining. T cell proliferation, methotrexate resistance, NK cell cytotoxicity, Treg cells and cytokine production by T cells were examined by flow cytometric assays. Patients were treated with and benefited from folinic acid. Studies revealed normal NK cell cytotoxicity, Treg cell counts, and naive-memory T cell percentages. Although SLC19A1 mRNA and protein expression were unaltered, remarkably, mitogen induced-T cell proliferation was significantly reduced at suboptimal folic acid and supraoptimal folinic acid concentrations. In addition, patients’ PBMCs were resistant to methotrexate-induced apoptosis supporting a functionally defective SLC19A1. This study presents the second pathogenic SLC19A1 variant in the literature, providing the first experimental evidence that functionally defective variants of SLC19A1 may present with symptoms of immunodeficiency.

Bartter syndrome and Gitelman syndrome are rare inherited tubulopathies characterized by hypokalemic, hypochloremic metabolic alkalosis. This study aimed to clarify the frequency of the phenotypic and genotypic subgroups, clinical features, long-term management, and prognosis of children diagnosed with Bartter syndrome and Gitelman syndrome in this study.Twenty-seven patients with Bartter syndrome and 6 patients with Gitelman syndrome, who were followed up between 2004 and 2020 in a single center, were included in the study.The median age of diagnosis was 4 months in patients with Bartter syndrome and 174 months in patients with Gitelman syndrome. At the last follow-up, a total of 12 Bartter syndrome patients had chronic kidney disease with a mean 7.79 ± 4.73 years of age; 5 (18.5%) of these patients had chronic kidney disease stage 2, 5 (18.5%) had chronic kidney disease stage 3, and 2 (7.4%) had chronic kidney disease stage 5. Of the 5 patients with Bartter syndrome with chronic kidney disease stage 2, 2 had CLCNKB and 1 had SLC12A1 gene mutation. Also, CLCNKB mutation was detected in 2 of 5 patients with Bartter syndrome with chronic kidney disease stage 3. Finally, 2 patients with Bartter syndrome with chronic kidney disease stage 5 had BSND mutation in one and CLCNKB mutation in the other. Estimated glomerular filtration rates of all patients with Gitelman syndrome were normal at the last follow-up. There was no statistically significant association of development of chronic kidney disease with genetic mutation, nephrocalcinosis, prematurity, and hypokalemia.Patients with Bartter syndrome and Gitelman syndrome may have a different clinical course due to the underlying genetic mutation. Bartter syndrome and Gitelman syndrome require lifelong treatment, and regular follow-up is important to prevent advanced-stage chronic kidney disease.

MELAS (Mitokondriyal Ensefalopati Laktik Asidoz Stroke Benzeri Epizodlar), multisistemik bir kas hastalığıdır. Klinik bulgular miyopati, göz bulguları, sensorinöral işitme kaybı, epilepsi, baş ağrısı, inme, endokrinopatiler ile prezente olur. Hastalıktan sorumlu mutasyonlar sıklık sırasına göre A3243G, T3271C, C3093G, A3252G, C3256T, A3260G, T3291C, T3308C, A13514G’dır. Bu makalede, farklı semptomlara sahip A3243G mutasyonu tespit edilen bir aileden altı MELAS’lı olgu, hastalığın klinik bulgularına dikkat çekilmek üzere sunulmuştur.

Primary immunodeficiency diseases (PID) are the diseases characterized by a dysfunction of the immune system. Affected patients share a different phenotype such as chronic infections, allergy, autoimmunity, and autoinflammation.In all, 433 children with PID were enrolled in this study. Clinical, laboratory, and demographic data of patients were reviewed retrospectively to investigate autoimmune and autoinflammatory complications. Autoinflammation in all patients with inflammation was confirmed by genetic analysis after excluding infectious etiology.Clinical features of 433 PID patients were evaluated retrospectively with long-term follow-up. Autoimmune disorders were identified in 69 (15.9%) patients with PID; 31 (45%) patients had a history of autoimmune disease before diagnosis of PID. The frequency of autoimmunity in immune dysregulation subgroup (76.6%) was higher than other forms of PID. The most common autoimmune manifestations were reported to be Addison's disease, hypoparathyroidism, and autoimmune hemolytic anemia. Autoinflammation were identified in 22 of the 433 (5.1%) patients with PID, including hyper immunoglobulin D syndrome (n = 9), Aicardi-Goutieres syndrome 1 (n = 6), adenosine deaminase 2 deficiency (n = 3), Blau syndrome (n = 2), tumor necrosis factor (TNF) receptor-associated periodic syndrome (n = 1), and auto-inflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation syndrome (n = 1).It is important to recognize association between autoimmunity, autoinflammation, and PID, which in the future could be useful for increased awareness and early diagnosis for these diseases.

Amaç: Çalışmamızda epilepsi ve anlıksal yetiyitimlerinde ilk basamak tanı testi olarak moleküler karyotipleme yapmayı ve bu hastalıklar ile ilişkisini ortaya koymayı amaçladık.Gereç ve Yöntem: Çukurova Üniversitesi Balcalı Hastanesi Tıbbi Genetik Polikliniği'ne başvuran ve geniş bir klinik problem yelpazesi sergileyen 580 hastaya Affymetrix CytoScan platform aracılı moleküler karyotipleme yapıldı.Bulgular: Moleküler karyotipleme sonucunda anlıksal yetiyitimi olan hastaların %41’inde mikrodelesyon, %32’sinde duplikasyon ve %50’sinde hem delesyon hem de duplikasyon tespit edildi. Epilepsi hastalarının %16’sında mikrodelesyon, %34’ünde duplikasyon ve %50’sinde delesyon ve duplikasyon; anlıksal yetiyitiminin eşlik ettiği epileptik hastalarda %33.3 mikrodelesyon, %44.4 duplikasyon ve %22.2 hem delesyonlar hem de duplikasyon bulundu. Ayrıca, bu çalışmada bir epileptik hastada uniparental dizomi ve 2 hastada marker kromozom saptandı. Sonuç: Elde edilen sonuçlar, moleküler karyotipleme tekniğinin klinik rutinde uygulanmasının ve elde edilen verilerin tıbbi genetik uzmanı tarafından yorumlanmasının kromozom düzeyindeki anomalilerin veya sendromların tanınmasında faydalı olduğunu göstermektedir. Özellikle epilepsi ve anlıksal yetiyitimi olan hastaların tanısında ilk basamak tanı testi olarak moleküler karyotipleme tercih edilebilir., Purpose: The aim of this study was to investigate molecular karyotyping of epilepsy and intellectual disabilites and to reveal its relationship with these diseases. Materials and Methods: A total of 580 patients with a wide range of clinical problems underwent molecular karyotyping by Affymetrix CytoScan platform included in the study that were presented to Medical Genetics Policlinics of Balcali Hospital and Clinics, Cukurova University Faculty of Medicine. Results: Molecular karyotyping identified 41% microdeletions, 32% duplications and 50% both deletions and duplications in mental retardation patients; 16% microdeletion, 34% duplications and 50% both deletions and duplications in epilepsy patients; and 33.3% microdeletions, 44.4% duplications and 22.2% both deletions and duplications in mental retardation with epilepsy group. In addition, one of epilepsy group with uniparental disomy and 2 marker chromosomes were detected in this study. Conclusion: Our results demonstrate that molecular karyotyping and clinical interpretation by a medical geneticist is efficient in diagnosing chromosomal diseases. Moreover, molecular karyotyping might be more effective as a first tier testing in epilepsy and psychomotor retardation patients.

Ailesel hipertrofik kardiyomiyopati (HKM) değişken klinik özellikler gösterebilen, otozomal dominant olarak ge- çen eksik penetranslı ve genetik olarak heterojen bir has- talıktır. Kalıtsal kardiyomiyopatilerin genetiği ile ilgili gün- cel gelişmeler, b #NAME?