ABSTRACT
BACKGROUND: Jervell and Lange-Nielsen syndrome (JLNS) isa recessive model of long QT syndrome which might also be related to possible hearing loss. Although the syndrome has been demonstrated to be originated from homozygous or compound heterozygous mutations in either the KCNQ1 or KCNE1 genes, additional mutations in other genetic loci should be considered, particularly in malignant course patients. CASE PRESENTATIONS: Three patients were admitted into hospital due to recurrent seizures/syncope, intrauterine and postnatal bradycardia respectively; moreover all three patients had congenital sensorineural hearing-loss. Their electrocardiograms showed markedly prolonged QT interval. Implantable defibrillator was implanted and left cardiac sympathetic denervation was performed due to the progressive disease in case 1. She had countless ventricular fibrillation and appropriate shock while using an implantable defibrillator. The DNA sequencing analysis of the KCNQ1 gene disclosed a homozygous c.728G > A (p.Arg243His) missense mutation in case1. Further targeted next generation sequencing of cardiac panel comprising 68 gene revealed a heterozygous c.1346 T > G (p.Ile449Arg) variant in RYR2 gene and a heterozygous c.809G > A (p.Cys270Tyr) variant in NKX2-5 gene in the same patient. Additional gene alterations in RYR2 and NKX2-5 genes were thought to be responsible for progressive and malignant course of the disease. As a result of DNA sequencing analysis of KCNQ1 and KCNE1 genes, a compound heterozygosity for two mutations had been detected in KCNQ1 gene in case 2: a maternally derived c.477 + 1G > A splice site mutation and a paternally derived c.520C > T (p.Arg174Cys) missense mutation. Sanger sequencing of KCNQ1 and KCNE1 genes displayed a homozygous c.1097G > A (p.Arg366Gln) mutation in KCNQ1 gene in case 3. ß-blocker therapy was initiated to all the index subjects. CONCLUSIONS: Three families of JLNS who presented with long QT and deafness and who carry homozygous, or compound heterozygous mutation in KCNQ1 gene were presented in this report. It was emphasized that broad targeted cardiac panels may be useful to predict the outcome especially in patients with unexplained phenotype-genotype correlation. Clinical presentations and molecular findings will be discussed further to clarify the phenotype genotype associations.
Subject(s)
Hearing Loss, Sensorineural/congenital , Jervell-Lange Nielsen Syndrome/genetics , KCNQ1 Potassium Channel/genetics , Polymorphism, Single Nucleotide , Adrenergic beta-Antagonists/therapeutic use , Child, Preschool , Electrocardiography , Female , Hearing Loss, Sensorineural/etiology , Heterozygote , High-Throughput Nucleotide Sequencing/methods , Homeobox Protein Nkx-2.5/genetics , Homozygote , Humans , Infant , Jervell-Lange Nielsen Syndrome/diagnosis , Jervell-Lange Nielsen Syndrome/drug therapy , Male , Pedigree , Potassium Channels, Voltage-Gated/genetics , Ryanodine Receptor Calcium Release Channel/genetics , Sequence Analysis, DNA/methods , TurkeyABSTRACT
OBJECTIVE: In this study we aimed to investigate the genotoxic effects of antineoplastic agents in occupationally exposed oncology nurses. Genotoxic effects mean the disruptive effects in the integrity of DNA and they are associated with cancer development. Biomonitoring of health care workers handling antineoplastic agents is helpful for the evaluation of exposure to cytostatics. PARTICIPANTS: The study included an exposed and two control groups. The exposed group (n=9) was comprised of oncology nurses. The first (n=9) and second (n=10) control groups were comprised of subjects who did not come into contact with antineoplastic drugs working respectively in the same department with oncology nurses and in different departments. METHODS: Genotoxicity evaluation was performed using SCE analysis. After applying culture, harvest and chromosome staining procedures, a total of 25 metaphases were analyzed per person. Kruskal Wallis test was used to perform statistical analysis. RESULT: A statistically significant difference of sister chromatid exchange frequencies was not observed between the exposed and control groups. CONCLUSION: Lack of genotoxicity in medical oncology nurses might be due to good working conditions with high standards of technical equipment and improved personal protection.
Subject(s)
Antineoplastic Agents/adverse effects , Occupational Exposure/prevention & control , Oncology Nursing , Sister Chromatid Exchange , Adult , Female , Health Facility Environment , Humans , Middle Aged , Protective Clothing , Ventilation , Young AdultABSTRACT
We investigated the association of cytokine gene polymorphisms with the development of chronic myelogenous leukemia (CML) and whether there is an association between gene polymorphisms Th1 and Th2 or regulatory- type cytokines and CML. Thirty patients with CML and 60 healthy controls were enrolled in this study. All genotyping (TNF-α, TGF-ß, IL-10, IL-6, and IFN-γ) studies were performed using sequence-specific primers PCR (PCR-SSP). Frequencies of IL-10 (-1082, -819, -592) GCC/ATA (p= 0.009) and IFN-γ; +874 T/A (p= 0.037) polymorphisms were significantly greater in the patients with CML. In contrast, significantly lower frequencies of the IFN-γ A/A (p= 0.004) genotype were observed in patients with CML compared with controls. The results suggest that the IL-10 GCC/ATA and IFN-γ T/A polymorphisms are potential risk factors, and that the IFN-γ A/A polymorphism is a protective factor, for CML in this study group.
