ABSTRACT
OBJECTIVE: Cardiac amyloidosis (CA) is a cardiomyopathy characterized by amyloid infiltration in the myocardium. Transthyretin cardiac amyloidosis (TTR-CA), commonly presenting as heart failure with preserved ejection fraction (HFpEF), was the focus of our study, which aimed to identify red flags that heighten suspicion of CA in HFpEF patients. METHODS: We prospectively included patients diagnosed with HFpEF. All patients were assessed for TTR-CA red flag features, cardiac and extra-cardiac, as outlined in the 'Diagnosis and Treatment of Cardiac Amyloidosis: A Position Statement of the European Society of Cardiology.' Technetium-99m pyrophosphate (99mTc-PYP) cardiac scintigraphy was performed in 167 HFpEF patients suspected of having TTR-CA. Patients testing positive and negative for TTR-CA were compared based on these red flag features. RESULTS: Out of 167 HFpEF patients, 19 (11.3%) were diagnosed with TTR-CA. In the TTR-CA group, 17 (89.5%) patients were 65 years or older. The presence of three or more red flags differentiated the TTR-CA positive and negative groups (P = 0.040). Features such as low voltage and pseudo infarct patterns were more prevalent in the TTR-CA group (P < 0.001 and P < 0.048, respectively). Left ventricular global longitudinal strain (LV-GLS) was lower in the TTR-CA positive group (P < 0.001). Multivariate analysis identified four variables-older age, pseudo infarct pattern, low/decreased QRS voltage, and LV-GLS-as strong, independent predictors of TTR-CA, with significant odds ratios (ORs) of 7.8, 6.8, 16.9, and 1.2, respectively. CONCLUSION: In this study, TTR-CA etiology occurs in approximately one in every ten HFpEF patients. The presence of three or more red flags increases the likelihood of TTR-CA. Older age, pseudo infarct pattern, low/decreased QRS voltage, and reduced LV-GLS are the most significant red flags indicating TTR-CA in HFpEF patients.
Subject(s)
Cardiomyopathies , Heart Failure , Stroke Volume , Humans , Female , Heart Failure/physiopathology , Heart Failure/diagnosis , Male , Aged , Stroke Volume/physiology , Prospective Studies , Middle Aged , Cardiomyopathies/physiopathology , Cardiomyopathies/diagnosis , Cardiomyopathies/diagnostic imaging , Amyloidosis/physiopathology , Amyloidosis/complications , Amyloidosis/diagnosis , Amyloidosis/diagnostic imaging , Amyloid Neuropathies, Familial/physiopathology , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/diagnostic imagingABSTRACT
Objective: Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes. To date, mutations have been identified in 14 different genes of patients with a clinical diagnosis of MODY. This study screened mutations in 14 MODY-related genes and the regulator factor X6 (RFX6) gene in children. Materials and Methods: The presence of clinical features of MODY and negative results for three autoantibody markers of T1DM in children and adolescents were used as inclusion criteria for genetic testing. The screening panel for next-generation sequencing included 14 MODY-related genes (GCK, HNF4A, HNF1A, HNF1B, PDX1, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8, KCNJ11, and APPL1) and the RFX6 gene. Results: Twenty-four different variants in MODY-related genes were identified in 49 children diagnosed with autoantibody-negative type 1 diabetes mellitus (T1DM). A 12 variants were classified as P/LP while 12 were interpreted as variant of unknown significance (VUS). Nine of the pathogenic or likely pathogenic variants were found in GCK, two in HNF1B, and one in ABCC8. Three variants were novel, and one was a de novo variant. All of the variants, except one, showed heterozygotic inheritance. Conclusion: This study screened mutations in the 14 MODY-related genes and the regulatory factor X6 (RFX6) gene in Turkish children diagnosed with autoantibody-negative type 1 diabetes mellitus (T1DM). The frequencies of the MODY subtypes differed from previous reports. Although GCK-MODY was the most frequent mutation in Turkish children, similar to previous studies, the second most prevalent MODY subtype was HNF1B-MODY. This study also established three additional novel mutations in different MODY genes.
ABSTRACT
Autoimmune polyendocrine syndrome type 1 (APS-1), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare monogenic autosomal recessive autoimmune disease. It is caused by mutations in the autoimmune regulator (AIRE) gene. APS-1 is diagnosed clinically by the presence of two of the three major components: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and primary adrenocortical insufficiency. A 3.3-year-old girl was presented with a carpopedal spasm to the pediatric emergency clinic. She had a history of recurrent keratitis, and chronic candidiasis as urinary tract infections and oral thrashes. Hypoparathyroidism (HPT) was diagnosed based on low serum concentrations of calcium and parathyroid hormone and elevated serum concentrations of phosphate, and treatment with calcium and calcitriol supplementation was started. Genetic testing revealed homozygosity for nonsense c.769C>T (p.R257X) mutation in exon 6 in the AIRE gene which was reported previously. At the age of 5.6 years, she was presented with an adrenal crisis, and treatment with hydrocortisone and fludrocortisone was started. The reported case highlights that unexplained chronic keratitis in children may be the first and most severe component of this syndrome. The classic triad of APS-1 may also appear in the first decade of life.
ABSTRACT
BACKGROUND/AIMS: Pancreatitis is one of the leading causes of digestive system-related hospital admissions, and it has a genetic background in a considerable portion of the patients. In this study, we aimed to investigate the genetic risk factors of idiopathic pancreatitis in Turkish patients and the contribution of copy number variations to the pathogenesis. MATERIALS AND METHODS: Idiopathic pancreatitis is defined as failure to detect risk factors despite comprehensive clinical assessments. Next-generation sequencing and multiple ligand-dependent probe amplification of PRSS1, SPINK1, CTRC, and CFTR were performed. For further genotype-phenotype correlations, patients were also questioned for the age of onset, family history, and pancreatic divisum. RESULTS: A total of 68 idiopathic pancreatitis cases were enrolled. Variants with potential clinical significance of PRSS1 were identified in 13.4%, SPINK1 in 6.3%, CTRC in 4.7%, and CFTR in 26.5% of the patients. No copy number variants were seen in any of these genes. At least 7.4% of the participants had complex genetic etiology involving 2 genes. CONCLUSIONS: At least 42.6% of the participants had a potential genetic risk factor. Five novel genetic variants were identified, and distinctive genetic risk factors of Turkish population were shown. The results showed that genetic etiology was frequent in pancreatitis and it was even more prominent in patients with early-onset disease. Considering that genetic risk factors may be informative for decisionmaking in the treatment options in addition to providing extensive prognostic value and familial genetic consultation; clinicians need to be more eager to offer genetic tests to pancreatitis patients.
Subject(s)
Pancreatitis, Chronic , Trypsin Inhibitor, Kazal Pancreatic , Humans , Mutation , Trypsin Inhibitor, Kazal Pancreatic/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , DNA Copy Number Variations , Trypsin/genetics , Genetic Predisposition to DiseaseABSTRACT
OBJECTIVE: Direct current electrical cardioversion (DCCV) is an effective rhythm-control option for patients with atrial fibrillation (AF). Despite initial success, a high recurrence rate remains a significant challenge. There is limited data on the genetic predictors of AF recurrence following successful DCCV. In this study, we aimed to evaluate whether 11 single nucleotide polymorphisms (SNPs) previously associated with AF are also linked to recurrence after DCCV in the Turkish population. METHODS: Seventy-five patients with persistent AF, who achieved stable sinus rhythm following DCCV, were included in the study. The patients were prospectively monitored for the onset of AF recurrence. Clinical characteristics and SNPs were analyzed and compared between patients who experienced recurrence and those who did not. RESULTS: The average age of the patients was 61.9 ± 11.5, and 33 (44%) were female. Over an average follow-up period of 17.0 (11.0-25.0) months, AF recurrence was observed in 38 patients (50.7%). A SNP in the PITX2 gene (rs17570669) (OR: 9.00, 95% Confidence Interval (CI): 1.28-63.02) and another in the ZFHX3 gene (rs2106261) (OR: 8.96, 95% CI: 1.03-77.66) were notably associated with AF recurrence in the additive model (P = 0.027 and 0.047, respectively). Multivariate Cox regression analysis revealed that the rs17570669 SNP was the sole independent predictor of AF recurrence (Hazard Ratio (HR): 3.59, 95% CI: 1.05-12.21, P = 0.040). CONCLUSION: The SNP in the paired-like homeodomain 2 (PITX2) gene (rs17570669) emerges as an independent predictor for AF recurrence after successful electrical cardioversion.
Subject(s)
Atrial Fibrillation , Humans , Female , Male , Atrial Fibrillation/genetics , Atrial Fibrillation/therapy , Electric Countershock , Polymorphism, Single Nucleotide , Chromosomes , RecurrenceABSTRACT
Objective: Chronic myeloid leukemia (CML) is a clonal hematologic disorder characterized by t(9;22) translocation, in which cytogenetic aberrations can occur in Ph(+) and (-) clones. These aberrations develop due to clonal evolution as well as treatment and they have prognostic significance. They are grouped as major and minor route anomalies in terms of their effects on prognostic parameters, such as treatment response, overall survival (OS), disease stage, complete cytogenetic response (CCyR), and major molecular response (MMR). It is stated that major route anomalies have unfavorable prognostic effects compared to minor route anomalies. We aimed to investigate the frequency and prognostic effects of cytogenetic anomalies detected in Ph(+) and (-) clones. Materials and Methods: In this study, we retrospectively analyzed the cytogenetic results of 450 patients diagnosed with CML between 2005 and 2020. Results: We detected cytogenetic aberrations in Ph-positive and negative clones in 41 of 450 patients. The most common anomalies were trisomy 8 (+8), additional Ph chromosome (+Ph), and loss of chromosome Y. Rarely, aneuploidy of the Y chromosome, dup (22), +11, and +6 were seen in CML patients. We observed that these identified aberrations negatively affected MMR and CCyR, and generally resulted in changing imatinib treatment for second-generation tyrosine kinase activity inhibitors. Our results are compatible with the literature. Conclusion: We suggest that cytogenetic aberrations detected in Ph(+) and (-) clones should be a warning sign in terms of treatment and require close observation. The use of cytogenetic methods for the identification of these anomalies is also important.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Cohort Studies , Retrospective Studies , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Chromosome Aberrations , Clonal Evolution/geneticsABSTRACT
OBJECTIVES: The aim of our study was to define the genotype-phenotype correlations of mutations in the PAH gene among the Turkey's Central Anatolian region. METHODS: Demographic characteristics of 108 patients with hyperphenylalaninemia (HPA) and 94 patients whose diagnosis was confirmed by PAH gene analysis (Sanger DNA Sequence Analysis and Next-Generation Sequencing) were determined retrospectively. Blood phenylalanine levels were analyzed using the high-performance liquid chromatography method. RESULTS: Mild HPA-not-requiring-treatment (NT) was found in 50.9% of the patients, and a classical phenylketonuria (PKU) phenotype was found in 25.9%. Forty-seven types of variants were identified. The predominant variants were p.Ala403Val (9.9%), p.Ala300Ser (9.4%), and c.1066-11G>A (splicing) (9.4%). Missense mutations accounted for 68% of mutations and attenuated the clinical impact; splice variations were found in 14.8% of cases with severe features. The p.Thr380Met allele was specific to the mild HPA-NT group. The c.1066-11G>A (splicing) allele was associated with classical PKU, whereas the p.Arg408Trp allele was linked to severe symptoms. Three variations of unknown clinical significance were discovered: c.706+4A>T (splicing), c.843-5T>C (splicing), and p.Thr323=. Of these variants, the patient who was homozygous for the c.843-5T>C (splicing) allele related to the classical PKU phenotype. 70% of the patients who underwent tetrahydrobiopterin (BH4) test were responsive. Phenotypes that responded to BH4 treatment were mostly mild phenotypes. CONCLUSIONS: The PAH genotype is the main factor that determines the phenotype of PKU. Establishing the relationship between the identified genetic mutations and phenotypic characteristics will provide very important data for each patient in terms of the specific management style.
Subject(s)
Organic Anion Transport Protein 1/metabolism , Phenylalanine Hydroxylase , Phenylketonurias , Biopterins/therapeutic use , Genetic Association Studies , Genotype , Humans , Mutation , Phenotype , Phenylalanine Hydroxylase/genetics , Phenylketonurias/diagnosis , Retrospective Studies , Turkey/epidemiologyABSTRACT
NudE Neurodevelopment Protein 1 (NDE1) gene encodes a protein required for microtubule organization, mitosis, and neuronal migration. Biallelic pathogenic variants of NDE1 gene are associated with structural central nervous system abnormalities, specifically microlissencephaly and microhydranencephaly. The root of these different phenotypes remains unclear. Here, we report a 20-year-old male patient referred to our clinics due to severe microcephaly, developmental delay, spastic quadriplegia, and dysmorphic features. The cranial computed tomography revealed abnormal brain structure and excess of cerebrospinal fluid, consistent with microhydranencephaly. A homozygous c.684_685del, p.(Pro229TrpfsTer85) change in NDE1 gene was found by clinical exome analysis. The variant has previously been reported in individuals with microlissencephaly, therefore we propose that the same variant within the gene may cause either microlissencephaly or microhydranencephaly phenotypes. There are only a few papers about NDE1-related disorders in the literature and the patient we described is important to clarify the phenotypic spectrum of the disease.
Subject(s)
Hydranencephaly , Lissencephaly , Microcephaly , Humans , Hydranencephaly/diagnosis , Hydranencephaly/genetics , Lissencephaly/diagnosis , Lissencephaly/genetics , Male , Microcephaly/diagnosis , Microcephaly/genetics , Microtubule-Associated Proteins/geneticsABSTRACT
Deletion 13q [del(13q)] is a favorable prognostic marker if it is detected as a sole abnormality in chronic lymphocytic leukemia (CLL). However the clinical courses of cases with isolated del(13q) are quite heterogeneous. In our study, we investigated copy number variations (CNVs), loss of heterozygosity (LOH), and the size of del(13q) in 30 CLL patients with isolated del(13q). We used CGH+SNP microarrays in order to understand the cause of this clinical heterogeneity. We detected del(13q) in 28/30 CLL cases. The size of the deletion varied from 0.34 to 28.81 Mb, and there was no clinical effect of the deletion size. We found new prognostic markers, especially the gain of 16p13.3. These markers have statistically significant associations with short time to first treatment and advanced disease stage. Detecting both CNVs and LOH at the same time is an advantageous feature of aCGH+SNP. However, it is very challenging for the array analysis to detect mosaic anomalies. Therefore, it is very important to confirm the results by FISH. In our study, we detected approximately 9% mosaic del(13q) by microarray. In addition, the gain of 16p13.3 may affect the disease prognosis in CLL. However, additional studies with more patients are needed to confirm these results.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 13/genetics , Chromosomes, Human, Pair 16/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Aged , DNA Copy Number Variations/genetics , Female , Humans , Loss of Heterozygosity/genetics , Male , PrognosisABSTRACT
BACKGROUND: In addition to risk factors such as low birth weight and uncontrolled oxygen therapy, genetic predisposition is also thought to play a role in the development of retinopathy of prematurity (ROP). In our study, we aimed to analyze single-nucleotide polymorphisms (SNPs) in VEGFA, EPAS1, BDNF and NOS3 genes in infants who develop ROP. MATERIALS AND METHODS: Seventy-five mild-moderate and 73 severe ROP cases were included in this study. Eleven different SNPs regions that located in VEGFA, EPAS1, BDNF and NOS3 genes were analysed by SnapShot technique and compared between two groups by the multiple logistic regression analysis. RESULTS: Statistically significant results were obtained in 8 of the 11 SNPs. It was observed that the excess of mutant alleles in four (VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744) of these regions increased ROP severity and treatment requirement (p < .001, p < .001, p = .022, p = .004, respectively) while the excess of mutant alleles in the other four regions (VEGFA rs833061, BDNF rs7929344, EPAS1 rs1867785 and rs1868085) showed that ROP severtiy was milder and eliminated the need for treatment (p < .001, p = .019, p = .017, p = .017, respectively). CONCLUSIONS: Considering the results of our study, it was seen that besides the known environmental and demographic factors in ROP pathogenesis, genetic predisposition also had an effect on the clinic and course of ROP. Polymorphisms of VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744 were found to be associated with severe ROP. More studies involving different populations cases are needed to confirm these findings and enlighten the etiology of ROP.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/genetics , Brain-Derived Neurotrophic Factor/genetics , Nitric Oxide Synthase Type III/genetics , Polymorphism, Single Nucleotide/genetics , Retinopathy of Prematurity/genetics , Vascular Endothelial Growth Factor A/genetics , Alleles , Female , Follow-Up Studies , Gene Frequency , Gestational Age , Humans , Infant , Infant, Newborn , Male , Retinopathy of Prematurity/diagnosis , Risk FactorsABSTRACT
Biphenotypic acute leukemias (BAL) are known as a type of leukemia involving cells with myeloid and along with lymphoid origin, in which genomic changes are detected. It has been stated that the most common genomic changes in BAL are t(9;22) and the translocations of the 11q23 region, these anomalies cause poor prognostic effects. We detected trisomy 5 (+5) in addition to the double Ph chromosome in a case where we investigated the genomic changes using molecular and conventional cytogenetic methods. Bone marrow transplantation was planned due to the poor response to prednisone. According to the information we have obtained, our report will be the first article to discuss the aberrations found in addition to the Ph chromosome in BAL and the effect of these aberrations on prognosis. However, the double observation of the Ph chromosome, which has a poor prognostic effect, is expected to affect the prognosis more negatively, this case will contribute to the literature in terms of trisomy 5. We think that more case reports are needed to reveal the anomalies and their prognostic significance in BAL.
Subject(s)
Chromosome Aberrations , Cri-du-Chat Syndrome/genetics , Gene Rearrangement , Leukemia, Biphenotypic, Acute/genetics , Leukemia, Biphenotypic, Acute/pathology , Philadelphia Chromosome , Trisomy/genetics , Child, Preschool , Chromosomes, Human, Pair 5/genetics , Humans , Male , PrognosisABSTRACT
BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathy characterized by lifelong gluten intolerance. Interleukin-15 (IL- 15) is a proinflammatory cytokine that is considered a key component in the immune reaction triggered by gluten. Our aim of this study was to evaluate the influence of IL-15 gene polymorphisms on CD development and clinical presentation. METHODS: The study was enrolled-with 90 CD patients (49 female/41 male, median years of age 11), their 38 siblings (20 female/18 male, median years of age 8), and 99 healthy controls (66 female/33 male, median years of age 13). Their demographic findings, symptoms, and signs histopathological grade, Human Leukocyte Antigen (HLA) types were recorded. IL-15 gene polymorphisms rs2857261, rs10519613, and rs1057972 were analyzed through PCR. RESULTS: There was a significantly higher frequency of GG genotype in rs2857972 polymorphisms and TT genotype in rs1057972 polymorphisms in celiac families compared to controls [41% vs. 23% (P = .0008), 36% vs. 11% (P = .001), respectively]. Without considering their HLA status, there was not any difference between celiacs and healthy siblings. However, when stratified according to their HLADQ2 status, rs2857972 GG polymorphism was 1.5 times prominent in celiacs than siblings at homozygous state, whereas rs1057972 TT genotype was found to be 2.5 times prominent in celiac siblings at heterozygous state. There was no association between these polymorphisms and clinical presentation. CONCLUSION: rs2857972 GG and rs1057972 TT variants of IL 15 are more prominent in celiac families than controls. However, the impact of IL-15 gene polymorphism on CD development is dependent on HLADQ2 status.
Subject(s)
Celiac Disease/diagnosis , Genetic Predisposition to Disease/genetics , Interleukin-15/genetics , Polymorphism, Genetic , Adolescent , Case-Control Studies , Celiac Disease/genetics , Child , Child, Preschool , Cohort Studies , Female , Genotype , Glutens , Humans , Male , Prospective Studies , SiblingsABSTRACT
AIM: To investigate relationship between refractive errors and eleven single nucleotide polymorphisms (SNPs) in HGF, GC, MFN1, GNB4, and VDR genes in Turkish population. METHODS: A group of 212 participants with myopia (n=91), hyperopia (n=45), and emmetropia (n=76) were investigated in this study. SNPs in HGF, GC, MFN1, GNB4 and VDR genes were studied by SnapShot technique. RESULTS: The patients in this study consists of 47 female/44 male (age: 23.47±4.30) patients with myopia, 20 female/25 male (age: 31.20±8.02) with hyperopia and 33 female/43 male (age: 25.22±6.60) with emmetropia. The genotype distribution of the rs7618348 polymorphism, which was the only statistically significant one between myopia and emmetropia group. The genotype distribution of the rs3819545, rs3735520, rs7041, and rs2239182 polymorphisms, which were statistically significant between hyperopia and emmetropia groups. CONCLUSION: The importance of genetic predisposition to refractive errors with respect to etiology of the disease is revealed. It is known that polymorphism studies may differ because of genetic diversity among populations so larger cohort studies are required in different populations to enlighten the etiology of the refractive errors.
ABSTRACT
Just as its clinical heterogeneity, genetic basis of Frontotemporal dementia (FTD) is also diverse and multiple molecular pathways are thought to be involved in disease pathogenesis. In the present study, FTD- related genes were evaluated in a Turkish cohort of 175 index FTD patients with a gene panel including GRN, MAPT, TARDBP, FUS, CHMP2B and VCP genes. Potential genetic associations were prospected in 16 patients (9.1%); five variants (p.(Gly35Glufs) and p.(Cys253Ter) in GRN; p.(Arg95Cys) in VCP; p.(Met405Val) in TARDBP and p.(Pro636Leu) in MAPT) were classified as pathogenic (P) or likely pathogenic (LP), in four familial and one sporadic patients. Three novel variants in MAPT, CHMP2B and FUS were also identified in familial cases. The most common pathogenic variants were observed in the GRN gene with a frequency of 1.14% (2/175) and this rate was 4.57% (8/175), including variants of uncertain significance (VUS). In this study with the largest cohort of Turkish FTD patients, GRN and MAPT variants were identified as the most common genetic associations; and rare causes like VCP, TARDBP, CHMP2B and FUS variants are recommended to be considered in patients with compatible clinical findings.
Subject(s)
Frontotemporal Dementia/epidemiology , Frontotemporal Dementia/genetics , Gene Frequency/genetics , Genetic Association Studies/methods , Genetic Variation/genetics , Progranulins/genetics , tau Proteins/genetics , Aged , Cohort Studies , DNA-Binding Proteins/genetics , Endosomal Sorting Complexes Required for Transport/genetics , Female , High-Throughput Nucleotide Sequencing/methods , Humans , Male , Middle Aged , RNA-Binding Protein FUS/genetics , Turkey/epidemiology , Valosin Containing Protein/geneticsABSTRACT
In acute myeloid leukemia, t(8;21) detected with a frequency of 10% is associated with good prognosis. However, variant t(8;21) is observed in 4% of these cases, and although the prognostic effects of these variant translocations have not been clearly revealed, there are findings that they affect the prognosis poorly. Here, we report on a 39 years old man, detected 4-way varyant t(8;21) which include relocalization of RUNX1/RUNX1T1 fusion gene, and loss of Y chromosome. RT-PCR also confirmed RUNX1/RUNX1T1 fusion transcript. Additionally, D820G and N822K mutations on KIT gene and mut B on NMP1 gene were detected. A complete remission could not achieved after first chemotherapy treatment. Due to primary resistance and variant of t(8;21), stem cell transplantation was performed. The variant translocation we have reported is unique and also the case is the second case that was reported in the literature in terms of the relocation of the AML1/ETO fusion gene. Since c-KIT mutations and LOY were also observed, it is not possible to predict the prognosis. To highlight the importance of variant translocations and relocalization of fusion gene, more cytogenetic and molecular data are needed.
Subject(s)
Chromosomes, Human/genetics , Core Binding Factor Alpha 2 Subunit/genetics , Oncogene Proteins, Fusion/genetics , RUNX1 Translocation Partner 1 Protein/genetics , Translocation, Genetic , Adult , Humans , Male , Metaphase/geneticsABSTRACT
OBJECTIVE: Genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF) and can predict AF recurrence after catheter ablation in different populations. However, there exists no such data for the Turkish population. We aimed to investigate whether 11 SNPs in the PITX2, ZFHX3, EPHX2, CAV1, TBX5, TGF-1, and SCN10A were related to AF and whether these SNPs can predict long-term atrial tachyarrhythmia (ATa) recurrence after pulmonary vein isolation (PVI) for AF in Turkish patients. METHODS: A total of 245 consecutive patients with non-valvular AF (44.9% men, mean age: 60.2±13.2 years, 65.3% paroxysmal AF) and 50 age- and sex-matched controls were included in this analysis. The clinical features and genetic variants were compared between the 2 groups. Of the 245 patients, 128 who underwent PVI with second-generation cryoballoon were further examined for long-term recurrence after the procedure. RESULTS: Four SNPs in PITX2 were significantly associated with AF (rs10033464_T: OR 3.29, 95%CI: 1.38-7.82, p=0.007; rs6838973_T: OR 3.06, 95% CI 1.36-6.87, p=0.007; rs3853445_C: OR 2.84, 95%CI: 1.27-6.36, p=0.011; rs17570669_T: OR 4.03, 95% CI: 1.71-9.51, p=0.001). Among these patients who underwent PVI, one locus in CAV1 (rs3807989_G: OR 4.50, 95% CI 1.04-19.31, p=0.043) and early recurrence (OR: 8.06, 95% CI: 2.12-30.55, p=0.002) predicted long-term AF recurrence after catheter ablation. CONCLUSION: Significant associations exists between 4 SNPs in PITX2 and AF (rs10033464, rs6838973, rs3853445, and rs17570669) in Turkish patients. In addition, 1 genetic variant in CAV1 (rs3807989) and early recurrence can predict long-term ATa recurrence after catheter ablation.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Aged , Atrial Fibrillation/genetics , Atrial Fibrillation/surgery , Female , Genome-Wide Association Study , Humans , Male , Middle Aged , NAV1.8 Voltage-Gated Sodium Channel , Pulmonary Veins/surgery , Recurrence , Treatment OutcomeABSTRACT
BACKGROUND: Deletion of 13q14 [del(13q)] is the most common cytogenetic change (50%) in chronic lymphoblastic leukemia (CLL), and it is a good prognostic factor if it is detected as a sole aberration by FISH. However, it is observed the clinical course of CLL cases with del(13q) are quite heterogeneous and the responsible for this clinical heterogeneity has not been established yet. Some investigators suggest type II deletion (include RB1 gene) is associated with more aggressive clinical course. Also, it is suggested that the deletion burden and the deletion type have a prognostic effect. In this study, we aimed to investigate the effect of RB1 gene deletion, deletion burden and deletion type on overall survival (OS), disease stage and time to first treatment (TTFT) in patients with isolated del(3q). Sixty eight cases, detected isolated del(13q) were included in the study. Also, RB1 deletion was analyzed from peripheral blood of them using FISH. RESULTS: RB1 deletion was detected in 41% of patients, but there was no statistically significant difference between RB1 deletion and TTFT, stage and OS (p > 0.05). At same time, statistically significant difference was detected between high del(13q) (> 80%) and TTFT (p < 0.05). CONCLUSION: The statistical analysis of our data regarding to the association between RB1 deletion and deletion type, TTFT, disease stage, and OS has not confirmed type II deletion or biallelic deletion cause poor prognosis. However, our data supports the deletion burden has a prognostic effect. More studies are needed to elucidate the cause of the clinical heterogeneity of CLL cases with del(13q).
ABSTRACT
S-adenosylhomocysteine hydrolase deficiency is an autosomal recessive neurometabolic disorder affecting the muscles, liver, and nervous system. The disease occurs by pathogenic variants of AHCY gene encoding S-adenosylhomocysteine hydrolase (AHCY) enzyme. This article reports a patient with presumed AHCY deficiency who was diagnosed by whole exome sequencing due to compound heterozygosity of novel p.T57I (c.170C>T) and p.V217M (c.649G>A) variants of AHCY gene. The patient had diffuse edema, coagulopathy, central nervous system abnormalities, and hypotonia. She died in 3 months due to cardiovascular collapse. Clinical findings of the present case were compatible with previously reported AHCY deficiency patients and the novel variants we found are considered to be the cause of the symptoms. This article also compiles the previous reports and expands clinical spectrum of AHCY deficiency by adding new features.
Subject(s)
Adenosylhomocysteinase/genetics , Amino Acid Metabolism, Inborn Errors/diagnosis , Glycine N-Methyltransferase/deficiency , Mutation , Amino Acid Metabolism, Inborn Errors/genetics , Female , Glycine N-Methyltransferase/genetics , Humans , Infant, Newborn , PrognosisABSTRACT
Mal de Meleda, also known as keratoderma palmoplantaris transgrediens, is a rare type of autosomal recessive palmoplantar keratoderma. A 19-year-old male presented with a congenital yellowish discoloration and thickening of both palms and soles of the feet. His family history revealed that there was no consanguinity between the mother and the father and that the patient had three healthy brothers. The second- and third-degree relatives, five females and one male, also exhibited similar skin findings. From the isolated DNA samples, the extrinsic regions of the SLURP1 gene were screened using the sequence analysis and the Sanger sequencing was performed with the 3130 Sequence Analyzer. Results of this analysis show that a p.Arg 96 Pro (R96P) (c.287 CGA>CCA) homozygous missense point mutation was detected on the SLURP 1 (a secreted toxin-like mammalian lymphocyte antigen 6/urokinase-type plasminogen activator receptor-related protein 1) gene of the patients, while heterozygous p.Arg 96 Pro (R96P) (c.287 CGA>CCA) mutation was detected in the mother, father, and brothers. Our search of the Human Genome Mutation Database and previous literature revealed no reports of this mutation in mal de Meleda. We report this case due to the identification of a novel gene mutation in a patient with mal de Meleda, a palmoplantar keratoderma.
ABSTRACT
Frontotemporal lobar degeneration (FTLD) describes a group of progressive brain disorders. The expansion of a noncoding GGGGCC (G4C2) hexanucleotide repeat in the C9orf72 gene is a major cause of both familial FTLD and amyotrophic lateral sclerosis. The aim of this study was to determine the prevalence of C9orf72 G4C2-repeat expansion in a Turkish population with FTLD and to determine its effects on the phenotype. The G4C2 expansion in the C9orf72 gene was analyzed in 100 cases of FTLD without mutations of the MAPT, PGRN, CHMP2B, VCP, TARDBP, and FUS genes and 100 age-matched healthy controls by using repeat-primed polymerase chain reaction and fragment length analysis techniques. A possible pathogenic repeat (≥30) was found in one of the familial cases (1/33), but none of the sporadic cases. The difference in the allele length between the cases and controls was statistically significant (p < 0.01). Intermediate (20-30) repeats were detected in 4% of our cases. Patients with psychotic symptoms appear to be enriched for intermediate and possibly pathogenic repeats. To determine whether the intermediate and ≥30-repeat allele carriers shared the C9orf72 risk haplotype, we examined rs4879515 and rs3849942 in all samples and family members of patients with possibly pathogenic alleles. We identified at least one risk allele for each single-nucleotide polymorphism in all intermediate and possibly pathogenic repeat carriers. We observed that ≥8 unit repeats were strongly correlated with the tagging risk alleles for both single-nucleotide polymorphisms (p < 0.001). To our knowledge, this is the first study to evaluate C9orf72 G4C2 repeats in Turkish patients with FTLD. The present findings suggest that pathogenic expansions of the C9orf72 repeat are uncommon in Turkish patients with FTLD, but intermediate repeats may be a risk factor for FTLD and act as a genetic modifying factor for psychotic symptoms.