Colorectal Cancer-Associated Genes Are Associated with Tooth Agenesis and May Have a Role in Tooth Development

Previously reported co-occurrence of colorectal cancer (CRC) and tooth agenesis (TA) and the overlap in disease-associated gene variants suggest involvement of similar molecular pathways. Here, we took an unbiased approach and tested genome-wide significant CRC-associated variants for association with isolated TA. Thirty single nucleotide variants (SNVs) in CRC-predisposing genes/loci were genotyped in a discovery dataset composed of 440 individuals with and without isolated TA. Genome-wide significant associations were found between TA and ATF1 rs11169552 (P = 4.36 × 10−10) and DUSP10 rs6687758 (P = 1.25 × 10−9), and positive association found with CASC8 rs10505477 (P = 8.2 × 10−5). Additional CRC marker haplotypes were also significantly associated with TA. Genotyping an independent dataset consisting of 52 cases with TA and 427 controls confirmed the association with CASC8. Atf1 and Dusp10 expression was detected in the mouse developing teeth from early bud stages to the formation of the complete tooth, suggesting a potential role for these genes and their encoded proteins in tooth development. While their individual contributions in tooth development remain to be elucidated, these genes may be considered candidates to be tested in additional populations

GG Polymorphism of Platelet ITGA2B Gene Increases the Magnitude of Interleukin-6 Release after Cardiopulmonary Bypass

Objective: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response which is thought to be a significant cause of postoperative organ dysfunction and mortality. In this study we aimed to investigate the effect of ITGA2B (integrin alpha 2b, platelet glycoprotein IIb of IIb/IIIa complex) gene polymorphism on the magnitude of inflammatory response after CPBMethods: Twenty patients undergoing coronary artery bypass grafting were included. Blood samples were taken at the three different times for analyses of Interleukin-6, Interleukin-10 and Nuclear Factor Kappa B by ELISA (t1: before operation, t2:10 minutes after removal of aortic cross clamping and t3: 24 hours after operation. ITGA2B gene polymorphisim, c.2621T&gt;G, resulting missense alteration, p.Ile874Ser (rs5911) was studied in patients and 27 healthy volunteers by targeted polymerase chain reaction (PCR) and restriction enzyme digestion. Perioperative organ dysfunction was evaluated by cardiac surgery&nbsp;scorring (CASUS) system.Results: There was no perioperative mortality. The mean ages of the patients and the controls were 67.45±12.30 and 51,38±7,03 years, respectively (p=0.001). Thirty-five percent (n=7) of the patients revealed TT, 45% (n=9) TG and 20% (n=4) GG polymorphism. The allele frequencies of the study group were similar to the controls (33,3%, n=9 revealed TT, 55,5 %, n=15 TG and 11,3%, n=3 GG). There was no&nbsp;significant difference in the frequency of genetic polymorphism between the patients and the controls. In the study group, patients with GG allele had signifi cantly higher interleukin 6 levels 24 hours after operation than the others (GG (338,14±22.20pg/ml) versus TT (306,14±22, 10 pg/ml), p=0.025, and GG versus TG (308, 12±14,50pg/ml), p=0.039).&nbsp;Conclusion: Our results reveal that GG allele of ITGA2B gene might have a significant role in the magnitude of the inflammatory response after CPB.&nbsp;</p

CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS

Objective: Radial ray defects (RRDs) are the most common congenital abnormality of the upper extremities, with a prevalence of 1:30,000. 70% of RRDs are syndromic or accompanied by additional malformations, whereas 30% are in isolated form. Definitive diagnosis is critical for follow-up and provides an opportunity for prenatal diagnosis. The aim of this study was to provide a guide for the differential diagnosis of patients with RRD via contributing to their molecular diagnosis by constructing a next-generation sequencing (NGS) gene-panel test

GJB2-RELATED NON-SYNDROMIC HEARING LOSS VARIANTS' SPECTRUM AND THEIR FREQUENCY IN TURKISH POPULATION

Objective: Hearing loss (HL) is one of the most prevalent chronic conditions in children and has consequences in speech, language, education, and social functioning which impede the quality of life. Due to the major involvement of the genetic factors in HL, especially non-syndromic HL (NSHL), genetic diagnosis and genetic counseling have a major impact on early management of the affected individuals and their families. Herein, we report the GJB2 gene variants and their frequencies in NSHL cohort at a tertiary health center between 2002-2021 to contribute for the future genetic counseling of Turkish NSHL patients

Osteogenesis imperfecta in 140 Turkish families: Molecular spectrum and, comparison of long-term clinical outcome of those with COL1A1/A2 and biallelic variants

© 2021Background: Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous group of diseases characterized by increased bone fragility and deformities. Although most patients with OI have heterozygous mutations in COL1A1 or COL1A2, 17 genes have been reported to cause OI, most of which are autosomal recessive (AR) inherited, during the last years. The aim of this study is to determine the mutation spectrum in Turkish OI cohort and to investigate the genotype-phenotype correlation. Methods: 150 patients from 140 Turkish families with OI phenotype were included in this study. Mutations in OI-related genes were identified using targeted gene panel, MLPA analysis for COL1A1 and whole exome sequencing. 113 patients who had OI disease-causing variants were followed for 1–20 years. Results: OI disease-causing variants were detected in 117 families, of which 62.4% in COL1A1/A2, 35.9% in AR-related genes. A heterozygous variant in IFITM5 and a hemizygous in MBTPS2 were also described, one in each patient. Eighteen biallelic variants (13 novel) were identified in nine genes (FKBP10, P3H1, SERPINF1, TMEM38B, WNT1, BMP1, CRTAP, FAM46A, MESD) among which FKBP10, P3H1 and SERPINF1 were most common. The most severe phenotypes were in patients with FKBP10, SERPINF1, CRTAP, FAM46A and MESD variants. P3H1 patients had moderate, while BMP1 had the mild phenotype. Clinical phenotypes were variable in patients with WNT1 and TMEM38B mutations. We also found mutations in ten genes (PLS3, LRP5, ANO5, SLC34A1, EFEMP2, PRDM5, GORAB, OCRL1, TNFRSF11B, DPH1) associated with diseases presenting clinical features which overlap OI, in eleven families. Conclusion: We identified disease-causing mutations in 83.6% in a large Turkish pediatric OI cohort. 40 novel variants were described. Clinical features and long-term follow-up findings of AR inherited OI types and especially very rare biallelic variants were presented for the first time. Unlike previously reported studies, the mutations that we found in P3H1 were all missense, causing a moderate phenotype