The Molecular Spectrum of Beta Thalassemia Mutations in Southeastern, Turkey

Objective: Beta-thalassemia (I3-thalassemia), which is very common in southern Turkey, is an autosomal recessive genetic disease caused by more than 400 mutations in the Beta-globin (HBB) gene. We aimed to investigate the beta thalassemia mutation profile in this region and contribute to treatment strategies with the study we conducted from patients who applied to our Genetic Diagnosis Center from Gaziantep and its surrounding southeast Anatolian provİnces. Method: In the study, HBB gene mutations were investigated by DNA sequence analysis in 313 unrelated patients who applied to our center. 41% of the patients included in the study were from Syrian migrant families. Results: A total of 32 different beta globin mutations were detected. The most common mutations are: IVS-I-110 G>A (HBB: c.93-21G>A) 20.65%, Codon 39 C>T (HBB: c.118C>T) 8.63%, IVS I-6 T>C (HBB: c.92+6T>C) 7.10%, IVS I-1 G>A (HBB: c.92+1G>A), 6.88%, IVS II-1 G>A (HBB: c.315+1G>A) 6.24%, Codon 6 (GAG>GTG) (HbS) (HBB: c.20A>T) 4.52%, CAP +20 C>T (HBB: c.-31C>T) 4.52%, Codon 8 (-AA) (HBB: c.25_26del) 4.30%,-30 (T>A) (HBB: c.-80T>A) 4.09%, IVS II-745 C>G (HBB: c.316-106C>G) 3.87%. We also detected a new variation (HBB: c.92+56G>A) that was not reported before, and six different beta globin gene mutations (HBB: c.90C>T, HBB: c.47G>A, HBB: c. 93-22_95del, HBB:c.30dup, HBB: c.180G>A , HBB: c.316-30A>C) not previously reported in Turkey. Four of these mutations were detected in Syrian patients (c.90C>T, c.47G>A, c.93-22_95del, c.30dup). Conclusion: Our study reveals that the mutations that cause beta thalassemia and hemoglobinopathies in the Southeast Anatolia region, which includes Gaziantep and its surrounding provİnces, are quite diverse and show some differences compared to other regions

İnfertil erkek hastalarda karyotip analizi ve Y kromozom mikrodelesyon analiz sonuçları

Amaç: İnfertilite çiftlerin %15’inde görülen bir problemdir. Oligozoospermi ve azoospermi kaynaklı erkek infertilitesi tanısı alanların %30’unun etiyolojisinde genetik nedenler sorumludur. Bu retrospektif çalışmada, merkezimize başvuran infertil erkeklerde yardımcı üreme teknikleri uygulanmadan önce hem kromozomal yapının belirlenmesi hem de Y kromozomu üzerindeki azoospermik faktör (AZF) bölgesinin mikrodelesyonunun belirlenmesi amaçlanmıştır. Gereç ve yöntem: Laboratuvarımıza rutin analizler için başvuran 675 hasta çalışıldı. Bu hastalardan konvansiyonel sitogenetik yöntemle periferik kandan kromozom analizi yapıldı ve Y kromozom mikrodelesyon belirleme kiti kullanılarak fragman analizi yöntemi ile Y kromozomu mikrodelesyonu araştırıldı. Bulgular: 675 hastanın 75’inde sitogenetik ve 21’inde moleküler, 2’sinde hem sitogenetik hem moleküler düzeyde anomali belirlendi. Anomalili karyotipe sahip hastalarda sayısal ve yapısal (resiprokal ve robertsonian tip translokasyon, inversiyon, ring kromozom gibi) anomaliler saptandı. Y mikrodelesyon belirlenen hastaların 2’sinde AZFa, 1 hastada AZFb, 13 hastada AZFc/d (c+ proksimal c), 6 hastada AZFb/c/d, 1 hastada AZFc/d ve kısmi AZFa bölgelerinde mikrodelesyon saptandı. Sonuç: Çalışmamız kromozom anomalilerinin ve Y kromozomu mikrodelesyonunun erkek infertilitesinin önemli bir nedeni olduğunu ve bu nedenle infertil hastalarda, kromozom analizi ve Y kromozomu mikrodelesyon testlerinin yapılmasının, erkek kaynaklı infertilitenin açıklanmasında gerekliliğini göstermektedir

Evaluation of the frequency of MEFV gene variants in patients with a pre-diagnosis of Familial Mediterranean Fever (FMF) in southeast Türkiye

Purpose: Familial Mediterranean Fever (FMF) is a hereditary auto inflammatory disease (MIM#249100). The most common symptoms are abdominal pain, high fever, and arthralgia. FMF is the result of variants in the MEditerraneanFeVer (MEFV) gene located on chromosome 16p13.3, which contains 10 exons and encodes the pyrin (marenostrin) protein. The frequency of MEFV gene variants that cause FMF varies according to ethnic groups, countries and even different regions in the same country. In our study, we aimed to determine the frequency and distribution of MEFV gene changes that cause Familial Mediterranean fever in southeast Türkiye. Materials and methods: A total of 6.660 patients with a pre-diagnosis of FMF, including 3.495 women and 3.165 men, were included in the study. Fragment analysis was performed to investigate the MEFV gene variants of the patients and the 19 most common variants in the Turkish population were examined. Results: We found at least one variant in 50.17% (3.341) of our 6.660 patients. In our patients, 108 different genotypes; in Exon 2, 3, 5 and 10 and we identified 16 different variants. We found 2.120 (63.21%) patients were heterozygous, 693 (20.74%) were compound heterozygotes, 275 (8.23%) were homozygous and 261 (7.81%) were complex genotypes. The five variants with the highest allele frequency are; R202Q (27.84%), M694V (22.83%), E148Q (21.98%), V726A (7.42%), and M680I (G>C) (6.39%). Conclusion: We identified the most common prevalence of MEFV gene alteration in a large patient group in our region. High R202Q mutation rates were among the remarkable results of this study. © 2023, Pamukkale University. All rights reserved

A new variant of the ıer3ıp1 gene: the first case of microcephaly, epilepsy, and diabetes syndrome 1 from Turkey

Microcephaly, Epilepsy, and Diabetes Syndrome 1 (MEDS1) is a rare autosomal recessive disorder and caused by defects in the IER3IP1 (Immediate Early Response 3 Interacting Protein 1) gene. Only 9 cases have been described in the literature. MEDS1 manifests as microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes. A simplified gyral pattern has been described in all cases reported to the date. Diagnosis is made by demonstration of specific mutations in the IER3IP1 gene. In this study, we present an additional case of a patient with MEDS1 who is homozygous for the c.53C >T p.(Ala18Val) variant. The case, the first to be reported from Turkey, differs from other cases due to the absence of a typical simplified gyral pattern on early brain MRI, the late onset of diabetes, and the presence of a new genetic variant. The triad of microcephaly, generalized seizures and permanent neonatal diabetes should prompt screening for mutations in IER3IP1