Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/ Computed Tomography in the Detection of Ovarian Cancer Recurrence in Patients with Elevated Serum Ca-125 Levels and Whether the Recurrence appears by Conventional Imaging

Introduction: We aimed in this study to evaluate the benefit of Fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the detection of ovarian cancer recurrence in a selected patient group who had elevated serum Ca-125 levels and whether the recurrence appears by conventional imaging.Material and Method: A total of 39 female patients (mean age: 59±12.3) who underwent 18F-FDG PET/CT for restaging of ovarian cancer due to of elevated serum Ca-125 levels were retrospectively included to this study. 18F-FDG PET/CT imaging have been performed for searching possible disease recurrence in 24 patients who had normal or undetermined abdominal CT or pelvic MRI (Group 1) and evaluating to extent of disease in 15 patients who had abnormal abdominal CT or pelvic MRI (Group 2). Disease recurrence was confirmed by histopathological examination of surgical procedures or clinical follow-up data for at least 6 months period.Results: The mean period between the completion of initial treatment and 18F-FDG PET/CT was 2.6±1.4 years. In 33 of the 39 patients (82%), recurrent disease was developed during the follow-up period. Of the 33 patients with recurrent disease, 6 (18%) were confirmed by histopathological examination, while in 27 (82%) were documented by clinical follow-up. The mean Ca-125 level and the SUVmax value of group 1 were 509 U/ml (range 50.3-6544 U/ml) and 12.26±4.9 (range 0-21.7), respectively. Overall sensitivity and specificity of 18F-FDG PET/CT in group 1 were quantified as 94% and 75%, respectively. The mean Ca-125 level and mean SUVmax value of group 2 at the time of 18F-FDG PET/CT scans were calculated as 358 U/ml (range 40.6-1233U/ml) and 11.4 ± 4.53 (range 4.5-20.1), respectively. Disease recurrence of 14 (93%) patients was correctly identified by 18F-FDG PET/CT. The sensitivity of 18F-FDG PET/CT in the detection of disease recurrence of group 2 was quantified as 100%. Specificity could not quantified due to absence of TN and FP results.Conclusions: 18F-FDG PET/CT has higher sensitivity and specificity in the detection recurrent ovarian cancer than serum Ca-125 levels and ceCT alone. The addition of 18F-FDG PET/CT to Ca-125 and ceCT improves the sensitivity of the evaluation of disease extension

Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/ Computed Tomography in the Detection of Ovarian Cancer Recurrence in Patients with Elevated Serum Ca-125 Levels and Whether the Recurrence appears by Conventional Imaging

Introduction: We aimed in this study to evaluate the benefit of Fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the detection of ovarian cancer recurrence in a selected patient group who had elevated serum Ca-125 levels and whether the recurrence appears by conventional imaging.Material and Method: A total of 39 female patients (mean age: 59±12.3) who underwent 18F-FDG PET/CT for restaging of ovarian cancer due to of elevated serum Ca-125 levels were retrospectively included to this study. 18F-FDG PET/CT imaging have been performed for searching possible disease recurrence in 24 patients who had normal or undetermined abdominal CT or pelvic MRI (Group 1) and evaluating to extent of disease in 15 patients who had abnormal abdominal CT or pelvic MRI (Group 2). Disease recurrence was confirmed by histopathological examination of surgical procedures or clinical follow-up data for at least 6 months period.Results: The mean period between the completion of initial treatment and 18F-FDG PET/CT was 2.6±1.4 years. In 33 of the 39 patients (82%), recurrent disease was developed during the follow-up period. Of the 33 patients with recurrent disease, 6 (18%) were confirmed by histopathological examination, while in 27 (82%) were documented by clinical follow-up. The mean Ca-125 level and the SUVmax value of group 1 were 509 U/ml (range 50.3-6544 U/ml) and 12.26±4.9 (range 0-21.7), respectively. Overall sensitivity and specificity of 18F-FDG PET/CT in group 1 were quantified as 94% and 75%, respectively. The mean Ca-125 level and mean SUVmax value of group 2 at the time of 18F-FDG PET/CT scans were calculated as 358 U/ml (range 40.6-1233U/ml) and 11.4 ± 4.53 (range 4.5-20.1), respectively. Disease recurrence of 14 (93%) patients was correctly identified by 18F-FDG PET/CT. The sensitivity of 18F-FDG PET/CT in the detection of disease recurrence of group 2 was quantified as 100%. Specificity could not quantified due to absence of TN and FP results.Conclusions: 18F-FDG PET/CT has higher sensitivity and specificity in the detection recurrent ovarian cancer than serum Ca-125 levels and ceCT alone. The addition of 18F-FDG PET/CT to Ca-125 and ceCT improves the sensitivity of the evaluation of disease extension

Association of protein function-altering variants with cardiometabolic traits:the strong heart study

Clinical and biomarker phenotypic associations for carriers of protein function-altering variants may help to elucidate gene function and health effects in populations. We genotyped 1127 Strong Heart Family Study participants for protein function-altering single nucleotide variants (SNV) and indels selected from a low coverage whole exome sequencing of American Indians. We tested the association of each SNV/indel with 35 cardiometabolic traits. Among 1206 variants (average minor allele count = 20, range of 1 to 1064), similar to 43% were not present in publicly available repositories. We identified seven SNV-trait significant associations including a missense SNV at ABCA10 (rs779392624, p= 8 x 10(-9)) associated with fasting triglycerides, which gene product is involved in macrophage lipid homeostasis. Among non-diabetic individuals, missense SNVs at four genes were associated with fasting insulin adjusted for BMI (PHIL, chr6:79,650,711, p= 2.1 x 10(-6); TRPM3, rs760461668, p= 5 x10(-8); SPTY2D1, rs756851199, p= 1.6 x 10(-8); and TSPO, rs566547284, p= 2.4 x 10(-6)). PHIL encoded protein is involved in pancreatic beta-cell proliferation and survival, and TRPM3 protein mediates calcium signaling in pancreatic beta-cells in response to glucose. A genetic risk score combining increasing insulin risk alleles of these four genes was associated with 53% (95% confidence interval 1.09, 2.15) increased odds of incident diabetes and 83% (95% confidence interval 1.35, 2.48) increased odds of impaired fasting glucose at follow-up. Our study uncovered novel gene-trait associations through the study of protein-coding variants and demonstrates the advantages of association screenings targeting diverse and high-risk populations to study variants absent in publicly available repositories

Recessive truncating NALCN mutation in infantile neuroaxonal dystrophy with facial dysmorphism

Background Infantile neuroaxonal dystrophy (INAD) is a recessive disease that results in total neurological degeneration and death in childhood. PLA2G6 mutation is the underlying genetic defect, but rare genetic heterogeneity has been demonstrated. One of the five families we studied did not link to PLA2G6 locus, and in the family one of the two affected siblings additionally had atypical features including facial dysmorphism, pectus carinatum, scoliosis, pes varus, zygodactyly and bilateral cryptorchidism as well as cerebellar atrophy, as previously reported

Autosomal recessive spastic paraplegia (SPG45) with mental retardation maps to 10q24.3-q25.1

Hereditary spastic paraplegias (HSPs) are characterized by progressive spasticity in the lower limbs. They are clinically heterogeneous, and pure forms as well as complicated forms with other accompanying clinical findings are known. HSPs are also genetically heterogeneous. We performed clinical and genetic studies in a consanguineous family with five affected members. A genome scan using 405 microsatellite markers for eight members of the family identified candidate gene loci, and subsequent fine mapping in 16 members identified the gene locus responsible for the HSP. The clinical manifestations were very early onset spastic paraplegia (SPG) accompanied by mental retardation and ocular signs. The gene locus was identified as the interval 102.05-106.64 Mbp on chromosome 10. Gene MRPL43 was analyzed in the patients. No mutation but high levels of mRNA were detected. We have mapped a novel autosomal recessive complicated form of HSP (SPG45) to a 4.6-Mbp region at 10q24.3-q25.1 with multipoint logarithm of odds scores > 4.5

A homozygous frameshift mutation of sepiapterin reductase gene causing parkinsonism with onset in childhood

We report two siblings that presented hypotonia and very early-onset parkinsonism. Homozygosity mapping using SNP genome scan data identified a candidate locus that was 12.2 Mega base pairs. By exome sequencing, we found a homozygous five-nucleotide deletion (c.448_452delAGAAC) in gene Sepiapterin Reductase (SPR). The mutation is predicted to lead to premature translational termination. Sepiapterin reductase deficiency (SRD) is a recently recognized dopa-responsive dystonia. Our findings show that SRD can manifest as early-onset parkinsonism, widening the spectrum of the disease phenotype and adding to the genetic heterogeneity of the disease. (C) 2011 Elsevier Ltd. All rights reserved

Desferrioxamine treatment of iron overload secondary to RH isoimmunization and intrauterine transfusion in a newborn infant

WOS: 000298655800015PubMed ID: 21735053Intrauterine transfusion is the standard of care in the management of severe Rh isoimmunization. Desferrioxamine has been used for the treatment of iron overload secondary to hemolysis and intrauterine transfusions in Rh isoimmunization cases. Here, we report a preterm infant born at 34 weeks of gestational age who had formerly received intrauterine transfusions for Rhesus hemolytic disease and presented with severe hyperferritinemia and elevated liver enzymes in the first week of life. Desferrioxamine treatment was started due to a ferritin level of 28,800 ng/ml and continued for 13 weeks. Although the treatment was successful, we observed resistant leukopenia which resolved after the cessation of treatment. In conclusion, iron overload secondary to intrauterine transfusions can be treated successfully with desferrioxamine; however, neonatologists must be aware of the possible side effects of this drug which has been used in only a limited number of newborns

Functional variants in cytochrome b5 type A (CYB5A) are enriched in Southwest American Indian individuals and associate with obesity

Objective This study aimed to identify genetic variants enriched in Southwest American Indian (SWAI) individuals that associate with BMI. Methods Whole genome sequencing data (n = 296) were used to identify potentially functional variants that are common in SWAI individuals (minor allele frequency ≥10%) but rare in other ethnic groups (minor allele frequency < 0.1%). Enriched variants were tested for association with BMI in 5,870 SWAI individuals. One variant was studied using a luciferase reporter, and haplotypes that included this variant were analyzed for association with various measures of obesity (n = 917-5,870), 24-hour energy expenditure (24-h EE; n = 419), and skeletal muscle biopsy expression data (n = 207). Results A 5′ untranslated region variant in cytochrome b5 type A (CYB5A), rs548402150, met the enrichment criteria and associated with increased BMI (β = 2%, p = 0.004). Functionally, rs548402150 decreased luciferase expression by 30% (p = 0.003) and correlated with decreased skeletal muscle CYB5A expression (β = −0.5 SD, p = 0.0008). Combining rs548402150 with two splicing quantitative trait loci in CYB5A identified a haplotype carried almost exclusively in SWAI individuals that associated with increased BMI (β = 3%, p = 0.0003) and decreased CYB5A expression, whereas the most common haplotype in all ethnic groups associated with lower BMI and percentage of body fatness, increased 24-h EE, and increased CYB5A expression. Conclusions Further studies on the effects of CYB5A on 24-h EE and BMI may provide insights into obesity-related physiology

Severe neurodegenerative disease in brothers with homozygous mutation in POLR1A

In two brothers born to consanguineous parents, we identified an unusual neurological disease that manifested with ataxia, psychomotor retardation, cerebellar and cerebral atrophy, and leukodystrophy. Via linkage analysis and exome sequencing, we identified homozygous c.2801C > T (p.(Ser934Leu)) in POLR1A ( encoding RPA194, largest subunit of RNA polymerase I) and c.511C > T (p.(Arg171Trp)) in OSBPL11 ( encoding oxysterol-binding protein- like protein 11). Although in silico analysis, histopathologic evidence and functional verification indicated that both variants were deleterious, segregation with the patient phenotype established that the POLR1A defect underlies the disease, as a clinically unaffected sister also was homozygous for the OSBPL11 variant. Decreased nucleolar RPA194 was observed in the skin fibroblasts of only the affected brothers, whereas intracellular cholesterol accumulation was observed in the skin biopsies of the patients and the sister homozygous for the OSBPL11 variant. Our findings provide the first report showing a complex leukodystrophy associated with POLR1A. Variants in three other RNA polymerase subunits, POLR1C, POLR3A and POLR3B, are known to cause recessive leukodystrophy similar to the disease afflicting the present family but with a later onset. Of those, POLR1C is also implicated in a mandibulofacial dysostosis syndrome without leukodystrophy as POLR1A is. This syndrome is absent in the family we present