Türk popülasyonunda oligozoospermi ve azospermi hastalarında infertilitenin genetik nedenleri

Objective: Advances in the science of genet- ics and the development of assisted reproductive techniques focus on the genetic causes of infer- tility. The aim of this research is to reveal genetic abnormalities in terms of sex chromosome aneu- ploidy and Y chromosome microdeletions. Material and Methods: A total of 350 patients with azoospermia or severe oligozoospermia were selected. After general examination of the patients and laboratory investigations were performed, cartoypes and Y chromosome microdeletions were examined. Results: A total of 225 infertile men with non-obstructive azoospermia (NOA) and 125 in- fertile men with oligozoospermia were enrolled into the study. The overall cytogenetic anomaly rate was 16%. Chromosomal changes were detected in 32 of 350 (9.1%) cases. The most common genetic anomaly was 47, XXY (Klinefelter syndrome) and the incidence was 11.5% in NOA group. This rate was 3.2% in oligozoospermia group. Y chromosome microdeletions were detected in 24 (6.8%) patients and similarly, it was observed more frequently in the NOA group than in the oligozoospermia group. Conclusion: The incidence of genetic causes have been increasing with the severity of infertil- ity. As a result, genetic screening and appropriate genetic counseling are needed before the use of assisted reproductive techniques.Amaç: Genetik bilimindeki ilerlemeler ve yardımcı üreme tekniklerindeki gelişmeler, infer- tilitenin genetik nedenlerine odaklanmamızı sağ- lamaktadır. Bu çalışmada, sex kromozomu anöplo- idisi ve Y kromozom mikrodelesyonları açısından genetik anormallikleriaraştırmayı amaçladık. Gereç ve Yöntemler: Azospermi veya şiddet- li oligozoospermi (≤ 5 milyon spermatozoa/ml) olan toplam 350 hasta analiz edildi. Hastalar genel muayene ve laboratuvar değerlendirmesi sonrası, karyotip ve Y kromozom mikrodelesyonu açısın- dan değerlendirildi. Bulgular: Non-obstrüktif azospermi (NOA) olan toplam 225 infertil erkek ve oligozoospermi olan 125 infertil erkek çalışmaya dahil edildi. Ge- nel sitogenetik anomali oranı% 16 idi. Üç yüz elli vakanın 32’sinde (% 9,1) kromozom değişiklikleri tespit edildi. En sık görülen genetik anomali 47, XXY (Klinefelter sendromu KS) idi ve insidansı NOA grubunda % 11.5 ve oligozoospermi gru- bunda % 3,2 idi. Y kromozom mikrodelesyonu 24 (% 6.8) hastada tespit edildi ve benzer şekilde NOA grubunda oligozoospermi grubuna göre daha sık görüldü (% 9.3 vs % 2.4, sırasıyla). Sonuç: İnfertilitenin şiddeti ile birlikte gene- tik nedenlerin görülme sıklığı artmaktadır. Sonuç olarak, yardımcı üreme tekniklerinin kullanılma- sından önce genetik tarama ve uygun genetik da- nışmanlığa ihtiyaç duyulmaktadır

Variant nonketotic hyperglycinemia caused by a novel pathogenic mutation in the glrx5 gene

Nonketotic hyperglycinemia (NKH) is caused by defects in the glycine cleavage system. Hyperglycinemia without biallelic mutations in one of the 4 genes that encode the constituents of the glycine cleavage system is classified as ‘variant NKH’. The defects in these cases are in the iron-sulphur cluster biogenesis and lipoate synthesis pathways. The GLRX5 gene is one of the genes in these new pathways. We report here an 8.5-year-old male patient presented with spasticity, ataxia and optic atrophy. He lost his ability to walk after a febrile infection at the age of 1.5 year. The patient’s cognitive functions were preserved. His plasma glycine level and cerebrospinal fluid/plasma glycine ratio were high. A novel homozygous mutation p.Gly116Asp (c.347G>A) in the GLRX5 gene was identified by whole exome sequencing. In conclusion, in a child, who have neurological regression, spasticity, ataxia, and whom cognitive functions are partially preserved, if plasma glycine level is high, variant NKH should be considered in the differential diagnosis

Molecular heterogeneity in cystic fibrosis

We aimed to evaluate type, frequency, and variety of pathogenic variants according to clinical and demographic features of children diagnosed with cystic fibrosis (CF). Twenty-five CF patients were evaluated retrospectively. Patients' demographics, physical examination, imaging, laboratory, and molecular pathogenic variant analysis findings were evaluated. Phe508del was the most frequently (33.3%) detected pathogenic variant, followed by point pathogenic variants E92K, 1898 + lGA/7T/7T, and 2789 + 5GA, respectively. Statistically higher rates of pathogenic variants were detected in male patients. The most frequently detected pathogenic variant was Phe508del. The identification of nine additional pathogenic variants of Phe508del revealed the heterogeneous nature of the CF

Multiple Symmetric Lipomatosis: Madelung's Disease

WOS: 000413898100012

Importance of diagnosis in breast cancer with Non-BRCA pathogenic germline variants of cancer susceptibility genes using high-throughput sequencing analysis

Objectives: The aim was to point out the importance of the diagnosis rate of breast cancer (BC) by analyzing the cancer predisposition genes except BRCA1/2 with multigene testing. Methods: In this study, 232 non-BRCA cases with BC and/or BC family history (FH) were analyzed using the next-gen-eration sequencing method. Results: Twenty-two different pathogenic/likely pathogenic variants were determined in 24 (10.34%) of cases, and these variants were detected in the CHEK2 (7/24, 29.1%), ATM (5/24, 20.8%), MUTYH (3/24, 12.5%), BLM (2/24, 8.3%), WRN (2/24, 8.3%), TP53 (1/24, 4.1%), BRIP1 (1/24, 4.1%), MSH2 (1/24, 4.1%), NBN (1/24, 4.1%), and PTEN (1/24, 4.1%) genes including three novel variants which were identified in the BLM, ATM, and MSH2 (3/22, 13.6%) genes. Fourteen of 24 (58.3%) cases had BC diagnosis, and 10 of 24 (41.6%) cases had a FH of BC. Conclusion: Among non-BRCA BC and/or BC FH cases, cancer susceptibility gene frequency was 10.34% in this study. CHEK2 and ATM genes had relatively high mutation rates

A genetic mimic of cerebral palsy: Homozygous NFU1 mutation with marked intrafamilial phenotypic variation

Background: Genetic defects in the NFU1, an iron-sulfur cluster scaffold protein coding gene, which is vital in the final stage of assembly for iron sulfur proteins, have been defined as multiple mitochondrial dysfunctions syndrome I. This disorder is a severe autosomal recessive disease with onset in early infancy. It is characterized by disruption of the energy metabolism, resulting in weak-ness, neurological regression, hyperglycinemia, lactic acidosis, and early death.Patient description: This report documents the case of a 27-month-old girl, who showed clinical signs and symptoms of spastic paraparesis with a relapsing-remitting course. The patient had a sister with a severe phenotype who died at the age of 16 months.Results: Magnetic resonance imaging revealed hyperintensity of the cerebral white matter that was more prominent in the frontal regions, with milder involvement in the posterior periventricular regions. There was also evidence of partial cystic degeneration and cavitation in the frontal regions. In addition, she had hyperglycinemia. Homozygous NM_001002755.4:c.565G>A (p.Gly189Arg) mutation was identified in the NFU1 gene; this had not previously been reported as homozygous.Conclusion: Hyperglycinemia and cavitating leukodystrophy are suggestive of an NFU1 mutation diagnosis. An intrafamilial phenotypic variation has not been published in NFU1-associated disorders before. Presenting with spasticity as a rare phenotype, NFU1 mutations could be considered a genetic mimic of cerebral palsy

Optical coherence tomography and fundus autofluorescence imaging in an infant with RD3-related leber congenital amaurosis

Background: Leber congenital amaurosis (LCA) is both genetically and phenotypically heterogeneous group of retinal disorder. Mutations in retinal degeneration 3 (RD3) have been reported as an infrequent cause of LCA which account for less than 1% of all known LCA cases. This case report provides Optical Coherence Tomography (OCT) and Fundus Autofluorescence (FAF) findings of an infant with LCA related to a mutation in RD3. Materials and Methods: Single retrospective case report. Results: TruSight One Expanded Sequencing Panel was applied to the patient on the Illumina NextSeq. Homozygous pathogenic variant (c.112 C > T, p.Arg38Ter) was detected in the RD3 gene. Well-demarcated central foveal atrophy was noted in the infrared imaging. FAF imaging showed perifoveal hyperautofluorescent ring and irregular hyperautofluorescence outside the vascular arcade. An arrest in foveal development and loss of outer retinal structure including outer nuclear layer, external limiting membrane, ellipsoid zone and interdigitation zone at the fovea were detected in the OCT imaging. Conclusion: This study indicates that RD3-related LCA has a very severe phenotype with foveal development arrest and very early loss of all photoreceptor layer and external limiting membrane at the fovea

Jinekolojik operasyonlarda postoperatif bakım ünitesinde kalış süresini etkileyen faktörler

Amaç: Bu retrospektif çalışmada elektif jinekolojik operasyon geçiren hastaların postoperatif bakım ünitesinde (POBÜ) kalma sürelerinin ve bunları etkileyen faktörlerin incelenmesi hedeflenmiştir.Gereç ve yöntem: Genel anestezi altında jinekolojik nedenlerle laparotomi yapılan, operasyonu 60 dakika ve üzerinde süren, rutin genel anestezi ve postoperatif analjezi uygulanmış, 18-80 yaş arası hastaların anestezi ve POBÜ kayıtları incelenmiştir. Hedef parametre olan POBÜ’nde kalış süresinin 60 dakika altında ya da üstünde oluşuna göre hastaların yaş, vücut kitle indeksi, operasyon süresi, ASA değeri, operasyon nedeninin patolojik özelliği, intraoperatif sıvı ve anestezik tüketimi, POBÜ’ne giriş Aldrete skoru, POBÜ’nde tedavi gereksinimi incelenmiştir.Bulgular: POBÜ’nde kalış süresinin ≥ 60 dakika olma olasılığının “American Society of Anesthesiologist” (ASA) fizik durum sınıflamasına göre ASA değeri ≥ III olanlarda 3,27, malign nedenli operasyonlarda 2,38, POBÜ’ne giriş Aldrete skoru < 9 olması halinde 3,28, solunum fizyoterapisi ve invazif mekanik ventilasyon gereksinimi durumunda sırasıyla 3,37 ve 14,6 kat arttığı bulunmuştur.Sonuç: Postoperatif bakım ve POBÜ kullanımı planlanırken, jinekolojik operasyon geçirecek hastalarda, ASA değeri ≥ III, patolojinin malign, POBÜ’ne giriş Aldrete skoru < 9 olmasının, solunum fizyoterapisi ve invazif mekanik ventilasyon gereksiniminin POBÜ’nde ≥ 60 dakika kalışa neden olabileceği göz önüne alınmalıdır.Anahtar kelimeler: Postoperatif derlenme, postoperatif bakım ünitesinde kalış, genel anestezi, jinekolojik operasyon

Comparison of screw fixation with elastic fixation methods in the treatment of syndesmosis injuries in ankle fractures

WOS: 000360122000005PubMed ID: 2611741417 patients with ankle syndesmosic injury were treated with a 4.5 mm single cortical screw fixation (passage of screw 4 cortices) and 15 patients were treated with single-level elastic fixation material. All patients were evaluated according to the AOFAS ankle and posterior foot scale at the third, sixth and twelfth months after the fixation. The ankle range of movement was recorded together with the healthy side. The Student's t test was used for statistical comparisons. No statistical significant difference was observed between the AOFAS scores (p > 0.05). The range of dorsiflexion and plantar flexion motion of the elastic fixation group at the 6th and 12th months were significantly better compared to the screw fixation group (p < 0.01). Elastic fixation is as functional as screw fixation in the treatment of ankle syndesmosis injuries. The unnecessary need of a second surgical intervention for removal of the fixation material is another advantageous aspect of this method of fixation