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Advanced genome sequencing technologies have provided us with the opportunity to deeply understand the mechanisms underlying conditions associated with the genome. There has been significant interest recently in understanding the characteristics of de novo mutations, which are genetic changes that arise in reproductive cells and are not present in parents, as well as the mechanisms involved in their occurrence. These mutations can be transmitted to subsequent generations and have the potential to influence genetic diversity and susceptibility to diseases, making this topic important. Due to limited studies in this area, the formation mechanisms and characteristic features of such mutations have not yet been fully understood. Background/Aims: In this study, we aimed to conduct a comprehensive analysis of de novo mutations in families undergoing trio clinical exome sequencing analysis. The objectives of the study were to investigate the relationship between parental ages and the frequency of de novo mutations, the distribution, prevalence, relationships, and molecular characteristics of de novo mutations. Methods: A total of 69 families who underwent Trio Clinical Exome Sequencing (CES) analysis at the Department of Medical Genetics, Faculty of Medicine, Selçuk University, between January 1, 2017, and December 31, 2023, were included in the study. DNA samples extracted from peripheral venous blood of individuals were sequenced using the Roche CES kit and DNBSEQ-G400™ sequencing device, and a total of 3892 genes were analyzed using the Seq Platform. Results: After analysis, 407 de novo variants were identified, with the majority being variants of unknown significance (55.28%). When examining the base change profile, the most common changes were found to be C -> G, G -> A, A -> G. The most commonly mutated genes were found to be DSPP, HPS4, VCL, and BMP4 genes. Conclusions: Correlation analysis revealed no significant relationship between parental age and the number of de novo mutations, and regression analysis showed that age was not a significant parameter in determining the number of de novo mutations

Background: Familial Mediterranean Fever (FMF) is an autoinflammatory disease and may express as various clinical findings. Chemokines are crucial elements of the inflammatory process. MCP-1 and its’ receptor CCR2 are the main chemokines for monocytes/macrophages that may play critical roles in FMF. Thus, it was aimed to investigate the MCP-1 (A-2518G) and CCR2 (G190A) polymorphisms and MCP-1 expression level, which may affect MEFV gene function. Material and Method: Patients with FMF were identified according to the Tel-Hashomer criteria. DNA and RNA were isolated from the obtained blood samples. Genotyping analysis was performed by PCR-RFLP technique. In addition, expression analyzes were performed by Real-time PCR method. The obtained results were evaluated statistically. Results: A total of 229 individuals (125 male and 104 female) were included in the study. While 120 individuals had FMF clinic, and 107 individuals did not have. The remaining two individuals had suspicious clinical status. In addition, while 75 individuals were homozygous mutants, 77 individuals were heterozygous mutants, and 77 individuals did not carry mutation in the MEFV gene. No significant relationship was found in between both FMF clinic and MEFV genotypes, and MCP-1 (A-2518G) and CCR2 (G190A) genotypes. In the expression analysis, MCP-1 expression increased in patients with FMF clinic compared to those without. In addition, MCP-1 expression was increased in the heterozygous MEFV group compared to those without mutation, moreover, the expression level was highest in homozygous MEFV group. In addition, according to the MCP-1 (A-2518G) genotyping, MCP-1 expression elevated in the homozygous as well as the heterozygous groups, compared to the Wild type group. Conclusion: MCP-1 expression is increased in FMF disease, which may explain the clinical differences between FMF patients. MEFV mutations may exacerbate inflammation by increasing MCP-1 transcription. MCP-1 expression is increased in patients with MCP-1(A-2518G) mutations, which aggravates FMF clinic. MCP-1 expression may be assessed as a marker in suspicious cases. Keywords: Familial Mediterranean Fever, MCP-1, CCR2, expression

Aim: The goal of this study was to investigate the expression of steroidogenic genes in ovine corpus luteum during early pregnancy. Materials and Methods: The animal model was designed as pregnancy; ewes were divided into three sub-groups, pregnancy 12th day: P12, pregnancy 16th day: P16, pregnancy 22th day: P22, and cyclic day 16 (C16). The expression of steroidogenic genes (steroidogenic acute regulatory protein; StAR, cytochrome P450 side-chain cleavage; P450sscc, and 3b-hydroxysteroid dehydrogenase/ delta5 delta4-isomerase; 3?HSD) was evaluated using qPCR, and mRNA localization of StAR was detected on P16 against C16 through in-situ hybridization. Results: The expression of StAR mRNA was higher on day P22 and P16 compared to P12 (p0,05). mRNA expression of P450scc was greater on day P22 and P16 than day P12 (p0,05). Also, mRNA expression of 3?HSD had a similar trend; it was higher on day P22 and P16 compared to P12 (p0,05). In in-situ hybridization, we did not detect StAR mRNA on cyclic day 16 (C16) while abundantly expressed in luteal cells in P16. Conclusion: The mRNA expression of steroidogenic genes may appear to play a critical role during early pregnancy in ewes. Accordingly, it can be suggested that the steroidogenic pathway in the corpus luteum of ewe may transcriptionally regulate progesterone synthesis required for maintenance of early pregnancy.

Treacher Collins syndrome (TCS) is a rare autosomal dominant congenital disorder characterized by various craniofacial malformations. The estimated incidence is 1 in 50000 live births. Bilaterally symmetric anomalies of the structure are present within the first and second branchial arches. Characteristic facial findings includes bilateral hypoplasia of the malar bones and mandible. This syndrome most commonly results from mutations in the TCOF1 gene. Here we present a five-year-old female patient with syndromic appearance and hearing loss. The patient had various facial dysmorphic features and malformed bilateral pinnae and left ear microtia. According to the clinical features, we suspected TCS and sequence analysis of TCOF1 gene was performed. A heterozygous new mutation c.1722_1731delCATCCTCCAG in exon 12 of the TCOF1 gene was detected. It has been determined that this mutation is pathogenic according to the in silico prediction tools. The current study further expands the TCOF1 mutation spectrum.

Papillophlebitis is known as central retinal vein occlusion seen in young patients. It usually presents as unilateral optic disc edema with cotton wool spots and hemorrhage in the peripapillary region. As it may be due to many autoimmune and inflammatory causes, a thorough systemic evaluation of the patient is warranted. In this case report we describe a bilateral, simultaneous papillophlebitis case thought to be related to hyperhomocysteinemia secondary to C677T polymorphism of methylenetetrahyrofolate reductase enzyme.

Ektrodaktili, ektodermal displazi, yarık dudak ve damak sendromu (EEC); ektrodaktili, ektodermal displazi ve orofasiyal yarık ile karakterize gelişimsel bir genetik hastalıktır. Literatürde bu konu ile ilgili çok fazla vaka rapor edilmemektedir. Sendromun esas komponentleri; el ve ayaklarda ektrodaktili ve sindaktili, normal veya yarık damaklı yarık dudak ve deri (hipopigmente ve kuru cilt, hiperkeratinoz, deri atrofisi), kıl (seyrek saç ve kaş), diş (küçük, yok veya displastik diş), tırnak( tırnak distrofisi) ve dış salgı bezleri ( terin azalması veya yokluğu, yağlı ve tükürük bezleri ) dahil olduğu anormal ektodermal yapılardır. Tedavisi; ortopedi, plastik ve diş cerrahisi, oftalmolojist, dermatolog ve konuşma terapisti ve psikologların birlikte çalışacağı multidisipliner bir yaklaşıma ihtiyaç duymaktadır. Biz literatürde ilk kez rastlanan hidrosefalili EEC sendromlu bir vakayı sunduk.

Sarkoidoz, nedeni tam olarak bilinmeyen ancak etiyolojisinde genetik, enfeksiyöz ajanlar, mesleksel maruziyet ve çevresel faktörlerin rol oynadığı multisistemik granülomatöz bir hastalıktır. Sarkoidozda ailesel yatkınlık bilinmekle beraber kalıtım şekli tam olarak tanımlanamamıştır. Bu makalede histopatolojik olarak sarkoidoz tanısı koyduğumuz iki kız kardeşi sunduk. Yapılan genetik incele- me sonucunda her iki kardeşte de Human Lökosit Antijen HLA HLA A24, B51, Cw07, DRB1 15, DQB1 06 genleri ortak olarak saptandı. Her iki olguya steroid tedavisi başlandı ve takibe alındı. Sonuç olarak her iki kız kardeşte tesbit edilen bulgulara göre sarkoidozda ailesel genetik yatkınlık olabileceği ve sarkoidoz tanısı alan bireylerin ailesinin sarkoidoz yönünden değerlendirilmesi gerektiği kanısına varıldı

This case report describes clinical examination and cytogenetic and molecular genetic analyses of a hermaphrodite mixed Maltese breed goat that was referred to the Gynecology Clinic of the Faculty of Veterinary Medicine, Selcuk University in 2010. In anamnesis, goat was a single kid at the birth and was polled. Clitoris was 1.9x0.9 cm in size and vagina was shorter than normal. By palpation and ultrasonographic examination, it was determined that the right (4.88 cm) and left (2.87 cm) testicles were located under skin in the inguinal region. Breast and nipples were in normal size. There was a rudimentary penis located under skin but no scrotum or prepitium was observed. After chromosome preparation using peripheral blood samples and GTG staining, appropriate metaphases were analyzed using an image analyzer program. Genomic DNA was isolated from the blood sample. Sexdetermining region Y (SRY) and amelogenin gene regions were amplified using polymerase chain reaction (PCR) including positive and negative controls. In karyotype analysis, metaphase plaque was observed as 60,XY. In PCR analysis, no SRY amplification was determined and only AMX allele was observed for amelogenin locus. Hermaphroditism is widely observed in goats and a number different mechanisms were reported. It is suggested that polled rams should be culled and karyotype and molecular genetics analyses should be performed to evaluate hermaphrodite cases in detail.

Abstract Background Adenoid tissue is a first‐line host defense secondary lymphoid organ, especially in childhood. The endoplasmic reticulum (ER) is required to maintain balanced cellular activity. With impaired ER functions, protein accumulation occurs, resulting in ER stress, which plays a role in the etiopathogenesis of many diseases. Objective We aimed to investigate the relationship between ER stress and adenoid tissue disorders, thereby elucidating the mechanisms of immunity‐related diseases. Methods Fifty‐four pediatric patients (>3 years old) who underwent adenoidectomy for chronic adenoiditis (CA) or adenoid hypertrophy (AH) were enrolled in this prospective, parallel‐group clinical study. Adenoids were divided into two groups (CA or AH) based on their size and evaluated for ER stress pathway and apoptosis pathway markers by Real‐time PCR and Western blot analysis. Results ER stress pathway markers significantly differed between the CA and AH groups. Children with CA had higher ER stress marker levels than the AH group (p

INTRODUCTION: Cervical cancer is the fourth most common cancer in worldwide and the leading cause of death among gynecological cancers. Neferine is a bisbenzylisoquinoline alkaloid isolated from the seed embryo of Nelumbo Nucifera. Studies have shown that Neferine has anticancer effects on a variety of human cancer cells. Neferine can induce apoptosis in cancer cells by various mechanisms. In this article; we aimed to show the apoptotic effects of neferin, a natural compound on HeLa cells. METHODS: In this experimental study, 1 human cervical cancer cell line and 1 human embryonic kidney cell line as a control group were used. Cell cultures were obtained from the American Type Culture Collection. 3-4,5-dimethyl-thiazolyl-2,5-diphenyltetrazolium bromide test was performed to determine the maximal inhibition concentration dose of neferin. Expression levels of apoptotic genes and antiapoptotic genes were determined by real-time polymerase chain reaction. The study was repeated in triplicate. RESULTS: The maximal inhibition concentration dose at which neferin inhibited the viability of human cervical cancer cells was determined as 20 micromol. Also, Neferin increased the level of apoptotic genes while decreasing the level of antiapoptotic genes. DISCUSSION AND CONCLUSION: Neferin induced apoptosis by activating the expression of apoptotic genes on human cervical cancer cells.

The presence of two different genetic conditions in the same individual is possible, especially in populations with consanguinity. In this case report, we present the coexistence of Artemis deficiency (OMIM 602450) and Three M (3M) syndrome (OMIM 273750). A 10-months-old male patient with neuromotor developmental delay was evaluated for immunodeficiency due to recurrent respiratory infections diarrhea and oral moniliasis from the age of 1.5 months. He had facial dysmorphism with rotated ears, flat nose and hypertelorism. Neurological examination revealed generalized hypotonia and mental motor delay. Immunological screening of the patient demonstrated mild lymphopenia, hypogammaglobulinemia, reduced number of CD3+ T cells (980 cells/mm3) and CD19+ B cells (35 cells/mm3). He was diagnosed with leaky T−B−NK+ SCID. Exome sequence analysis showed the presence of a homozygous pathogenic DCLRE1C variant [c.194C > T; p.T65I (NM_001033855)] and a homozygous pathogenic variant in OBSL1, a gene associated with 3M syndrome [c.3922C > T; p.R1308X (NM_001173431)]. Our proband died of sepsis and multiple organ failure. This case illustrates that different clinical findings in patients might not be explained with a single genetic defect, and consanguinity increases the change for coexistence of autosomal recessive diseases. Clinicians should consider exome sequencing to identify disease-causing mutations in patients with heterogeneity of clinical findings.

MicroRNA (miRNA) expression is a dynamic process in the cell, and the proper time period for post-transcriptional regulation might be critical due to the gene-on/-off expression times of the cell. Here, we investigated the effect of different time-points on proliferation, invasion and miRNA expression profiles of human breast cancer cell lines MCF-7 (non-metastatic, epithelium-like breast cancer cell line with oestrogen receptor (ER) positive (+) and human breast cancer cell lines MDA-MB-435 (metastatic, invasive, ER negative (-). For this purpose, MCF-7 and MDA-MB-435 cells were seeded different number in E-plate 16 for proliferation experiment using an electrical impedance-based real-time cell analyzer system (RTCA) for 168 h. Similarly, invasion potential of MCF-7 and MDA-MB-435 were determined by RTCA for 90 h. Total RNAs including miRNAs were isolated at 2, 4, 6, 12, 24, 48 h from the MCF-7 and MDA-MB-435 cells. Afterward, the quantitative 84 miRNA expressions of MCF-7 and MDA-MB-435 were analyzed by Fluidigm Microfluidic 96.96 Dynamic Array. The results of these study demonstrated that both proliferation potential and invasion capacity of MDA-MB-435 is higher than MCF-7 as time-dependent manner. Furthermore, we detected that up/down expressions of 32 miRNAs at all time points in MDA-MB-435 compared to MCF-7 (at least ten-fold increased). Because of the high number of miRNAs, we more closely evaluated the expression of six of them (miR-100–5p, miR-29a-3p, miR-130a-3p, miR-10a-5p, miR-10b-5p, miR-203a), and determined that their levels were dramatically changed by at least 50-fold at different time points of the experiment (p

Objectives: Appropriate antibiotic therapy and prevention of cross-contamination are the most important subjects in tuberculosis (TB) control. The aim of this study was to investigate the major phylogenetic clades and transmission rate of multidrug-resistant (MDR) Mycobacterium tuberculosis isolates (n = 200) from patients with TB in Sivas and Konya Provinces of Turkey. Methods: The phylogenetic relationship among the isolates was investigated by spoligotyping method. In addition, the 24-locus mycobacterial interspersed repetitive unit–variable-number tandem repeat (MIRU-VNTR) typing method was used to reveal cross-contamination. Results: Spoligotyping revealed 13 different spoligotypes. A total of 188 strains (94.0%) were included in the cluster. The most prominent spoligofamily was the T family (43.0% of strains), followed by LAM (26.0%), H (8.0%), X and S (both 6.0%) and U (5.0%). Also, 12 strains (6.0%) belonged to the Beijing profile. MIRU-VNTR results showed 176 (88.0%) different genotypes among the isolates. In total, 24 strains (12.0%) were in the cluster. Conclusions: According to spoligotyping, there is a heterogeneous M. tuberculosis population in Turkey. MIRU-VNTR results showed that cross-contamination observed between MDR M. tuberculosis isolates in Turkey is controllable.

Encephalitozoon cuniculi was first recognized as the disease agent in rabbits in 1922. The genotype of E. cuniculi isolated from laboratory rabbits with the neurologic disease was described as genotype I. In the eye, this parasite causes damage to the lens, causing phacoclastic uveitis and cataracts. Intraocular infection often occurs in cases of transplacental transmission. There has been no report on the molecular diagnosis of the parasite in Turkey. The current study is the first report on the detection of E. cuniculi spores using the molecular method in Turkey. In our previous study, a rabbit breeding facility was determined seropositive for E. cuniculi infection monitored for five years in terms of clinical symptoms. An autopsy was performed for a definite diagnosis of the infection. Samples were stained according to the hematoxylin-eosin (H&E) staining after tissue processing procedure and histopathologic analysis was performed. In addition to, the samples for DNA extraction were also taken during the autopsy. ECUNF and ECUNR species-specific primer pairs were used for amplification and genotyping of E. cuniculi. The animals were observed no clinical symptoms except ocular lesion (n=9). Therefore, one of these rabbits was used in the autopsy to definite diagnosis and determination of the damage to the eye. As histopathological, the lesions in the eye were found in the initial or middle stage of progressive infection. The DNA sequence showed that E. cuniculi examined in the present study were genotype I. Possible cause of the visible white mass in the rabbit"s eye may be the parasite infection. Therefore, clinicians may consider E. cuniculi as one of the possible causes of ocular lesions in rabbits during daily inspection or ophthalmological examination.

Ectrodactyly, ectodermal dysplasia, cleft lip, and palate syndrome (EEC) is a genetic developmental disorder characterized by ectrodactyly, ectodermal dysplasia and orofacial clefts (cleft lip/ palate). A few cases have been reported in literature. The cardinal components of the syndrome are ectrodactyly and syndactyly of the hands and feet, cleft lip with or without cleft palate, and abnormalities ectodermal structures including skin (i.e. hypopigmented and dry skin, hyperkeratosis, skin atrophy), hair (sparse hair and eye brows), teeth (small, absent or dysplastic teeth), nails (nail dystrophy) and exocrine glands (reduction/ absence of sweat, sebaceous and salivary glands). A multidisciplinary approach for treatment is needed which is co-ordinated by orthopedic, plastic, dental surgeons, ophthalmologist, dermatologists and speech therapists, psychologists. We presented EEC syndrome case with hydrocephaly by the literature. [Cukurova Med J 2013; 38(3.000): 531-535]