Rapid molecular diagnosis of ALB gene variants prevents unnecessary interventions in familial dysalbuminemic hyperthyroxinemia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Saygin Abali ◽  
Zehra Yavas Abali ◽  
Kanay Yararbas ◽  
Serap Semiz
Keyword(s):  
Molecular Diagnosis ◽  
De Novo ◽  
Hot Spot ◽  
High Serum ◽  
Thyroid Function Tests ◽  
Simple Method ◽  
Normal Thyroid Function ◽  
Frequent Variant ◽  
Euthyroid Hyperthyroxinemia ◽  
Dominant Condition

Abstract Objectives Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant condition caused by heterozygous gain-of-function mutations in the human ALB gene. Case presentation We report, a three-year-old boy with FDH due to p.R242P (or p.R218P without signal peptide) mutation in the ALB gene with a phenotype characterized by extremely high serum total and free thyroxine concentrations. His parents had normal thyroid function tests (TFT), so the mutation detected in this patient is assumed “de novo”. Although the most frequent variant was p.R242H in Caucasians and p.R242P in Japanese, our patient had p.R242P variant. Conclusions Early identification of FDH is fundamental to prevent unnecessary repeats of TFT with different methods. We encourage the ALB gene hot spot sequencing initially and indicate that this molecular diagnosis is a rapid and simple method to diagnose FDH in individuals with euthyroid hyperthyroxinemia.

Development of new predictive equations for basal metabolic rate in Iranian healthy adults: negligible effect of sex

2020 ◽  
pp. 1-10
Author(s):  
Bahareh Nikooyeh ◽  
Nastaran Shariatzadeh ◽  
Ali Kalayi ◽  
Maliheh Zahedirad ◽  
Tirang R. Neyestani
Keyword(s):  
Metabolic Rate ◽  
Thyroid Function ◽  
Basal Metabolic Rate ◽  
Age Groups ◽  
Thyroid Function Tests ◽  
Anthropometric Measures ◽  
Predictive Equations ◽  
Normal Thyroid Function ◽  
Asian People ◽  
Predictive Formulas

Abstract. Some studies have reported inaccuracy of predicting basal metabolic rate (BMR) by using common equations for Asian people. Thus, this study was undertaken to develop new predictive equations for the Iranian community and also to compare their accuracy with the commonly used formulas. Anthropometric measures and thyroid function were evaluated for 267 healthy subjects (18–60 y). Indirect calorimetry (InCal) was performed only for those participants with normal thyroid function tests (n = 252). Comparison of predicted RMR (both kcal/d and kcal.kg.wt−1.d−1) using current predictive formulas and measured RMR revealed that Harris-Benedict and FAO/WHO/UNU significantly over-estimated and Mifflin-St. Jeor significantly under-estimated RMR as compared to InCal measurements. In stepwise regression analysis for developing new equations, the highest r2 (=0.89) was from a model comprising sex, height and weight. However, further analyses revealed that unlike the subjects under 30 y, the association between age and the measured RMR in subjects 30 y and plus was negative (r = −0.241, p = 0.001). As a result, two separate equations were developed for these two age groups. Over 80 percent of variations were covered by the new equations. In conclusion, there were statistical significant under- and over-estimation of RMR using common predictive equations in our subjects. Using the new equations, the accuracy of the calculated RMR increased remarkably.

scholarly journals De Novo Design of Selective Quadruplex‐Duplex Junction Ligands and Structural Characterisation of their Binding Mode: Targeting the G4 Hot‐Spot

2020 ◽  
Author(s):  
Laura Díaz-Casado ◽  
Israel Serrano-Chacón ◽  
Laura Montalvillo-Jiménez ◽  
Francisco Corzana ◽  
Agatha Bastida ◽  
...  
Keyword(s):  
De Novo ◽  
Hot Spot ◽  
Binding Mode ◽  
De Novo Design ◽  
Structural Characterisation

scholarly journals Front Cover: De Novo Design of Selective Quadruplex–Duplex Junction Ligands and Structural Characterisation of Their Binding Mode: Targeting the G4 Hot‐Spot (Chem. Eur. J. 20/2021)

2021 ◽  
Vol 27 (20) ◽  
pp. 6101-6101
Author(s):  
Laura Díaz‐Casado ◽  
Israel Serrano‐Chacón ◽  
Laura Montalvillo‐Jiménez ◽  
Francisco Corzana ◽  
Agatha Bastida ◽  
...  
Keyword(s):  
De Novo ◽  
Hot Spot ◽  
Binding Mode ◽  
De Novo Design ◽  
Front Cover ◽  
Structural Characterisation

scholarly journals 762 A combination of functional biomarkers improves identification of the tumor-specific reactive T cell repertoire

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A810-A810
Author(s):  
Arianna Draghi ◽  
Katja Harbst ◽  
Inge Svane ◽  
Marco Donia
Keyword(s):  
T Cells ◽  
T Cell ◽  
De Novo ◽  
Autologous Tumor ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Simple Method ◽  
Functional Biomarkers

BackgroundDetecting the entire repertoire of tumor-specific reactive T cells is essential for investigating the broad range of T cell functions in the tumor-microenvironment. At present, assays identifying tumor-specific functional activation measure either upregulation of specific surface molecules, de novo production of the most common antitumor cytokines or mobilization of cytotoxic granules.MethodsIn this study, we combined transcriptomic analyses of tumor-specific reactive tumorinfiltrating lymphocytes (TILs), TIL-autologous tumor cell co-cultures and commonly used established detection protocols to develop an intracellular flow cytometry staining method encompassing simultaneous detection of intracellular CD137, de novo production of TNF and IFNy and extracellular mobilization of CD107a.ResultsThis approach enabled the identification of a larger fraction of tumor-specific reactive T cells in vitro compared to standard methods, revealing the existence of multiple distinct functional clusters of tumor-specific reactive TILs. Publicly available datasets of fresh tumor single-cell RNA-sequencing from four cancer types were investigated to confirm that these functional biomarkers identified distinct functional clusters forming the entire repertoire of tumor-specific reactive T cells in situ.ConclusionsIn conclusion, we describe a simple method using a combination of functional biomarkers that improves identification of the tumor-specific reactive T cell repertoire in vitro and in situ.

scholarly journals The T4:TBG Ratio: A Re-Evaluation with Particular Reference to Low and High Serum TBG Levels

1982 ◽  
Vol 19 (2) ◽  
pp. 101-103 ◽  
Author(s):  
E C Attwood ◽  
G E Atkin
Keyword(s):  
Retrospective Study ◽  
Thyroid Function ◽  
Reference Range ◽  
High Serum ◽  
Reference Ranges ◽  
Thyroid Function Tests ◽  
Thyroxine Binding Globulin ◽  
Biochemical Investigation ◽  
Small Increments ◽  
Routine Assay

The thyroxine: thyroxine-binding globulin (T4: TBG) ratio is now an established part of the biochemical investigation of thyroid function. Reference ranges have been reported for euthyroid subjects with TBG levels within the range 6–16 mg/l. Routine assay of TBG on all thyroid function tests in this laboratory has suggested that, in patients with low or high TBG levels, the established reference ranges for T4:TBG may not be strictly applicable. A retrospective study has been made of a large number of thyroid function requests, including serum total T4, free T4, TBG, and TSH assays. Evidence is presented to show that in subjects with a TBG level of less than 8 mg/l the reference range for T4: TBG is elevated. Similarly, in subjects with a TBG greater than 16 mg/l, the reference range for T4: TBG is lowered. The data suggest that it is necessary to quote a T4: TBG reference range based on small increments of TBG levels or to relate total T4 reference ranges to those increments.

scholarly journals X-linked hypophosphatemic rickets: Case report

2014 ◽  
Vol 142 (1-2) ◽  
pp. 75-78 ◽  
Author(s):  
Vladimir Radlovic ◽  
Zeljko Smoljanic ◽  
Nedeljko Radlovic ◽  
Zoran Lekovic ◽  
Dragana Ristic ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
De Novo ◽  
Serum Levels ◽  
High Serum ◽  
Hypophosphatemic Rickets ◽  
De Novo Mutation ◽  
Inherited Disease ◽  
X Ray ◽  
Phex Gene ◽  
Renal Tubular

Introduction. X-linked hypophosphatemic rickets (XLHR) is a dominant inherited disease caused by isolated renal phosphate wasting and impairment of vitamin D activation. We present a girl with X-linked hypophosphatemic rickets (XLHR) as a consequence of de novo mutation in the PHEX gene. Case Outline. A 2.2-year-old girl presented with prominent lower limb rachitic deformity, waddling gait and disproportionate short stature (79 cm, <P5; -1,85 SD). On the basis of hypophosphatemia, hyperphosphaturia, high serum level of alkaline phosphatase, normal calcemia, 25(OH)D and PTH, as well as characteristic clinical and X-ray findings, diagnosis of hypophosphatemic rickets (HR) was made. Normal calciuria and absence of other renal tubular disorders indicated HR as a consequence of isolated hyperphosphaturia. The treatment (phosphate 55 mg/kg and calcitriol 35 ng/kg per day), introduced 15 month ago, resulted in a stable normalization of alkaline phosphatase and phosphorus serum levels (with intact calcemia and calciuria), disappearance of X-ray signs of the active rickets and improvement of the child?s longitudinal growth (0.6 cm per month). Subsequently, by detection of already known mutation in the PHEX gene: c.1735G>A (p.G579R) (exon 17), XLHR was diagnosed. Analysis of the parental PHEX gene did not show the abnormality, which indicated that the child?s XLHR was caused by de novo mutation of this gene. Conclusion. Identification of genetic defects is exceptionally significant for diagnosis and differential diagnosis of hereditary HR.

scholarly journals A repetitive DNA fragment carrying a hot spot for de novo DNA methylation enhances expression variegation in tobacco and petunia

1995 ◽  
Vol 8 (6) ◽  
pp. 919-932 ◽  
Author(s):  
Michael ten Lohuis ◽  
Andreas Müller ◽  
Iris Heidmann ◽  
Ingrid Niedenhof ◽  
Peter Meyer
Keyword(s):  
Dna Methylation ◽  
Repetitive Dna ◽  
De Novo ◽  
Hot Spot ◽  
Dna Fragment

scholarly journals Molecular marker aided breeding for blast resistant rice in Nepal

2014 ◽  
Vol 15 ◽  
pp. 128-138
Author(s):  
Bal K Joshi ◽  
Hari P Bimb ◽  
Gopal Parajuli ◽  
Bedanand Chaudhary
Keyword(s):  
Resistance Gene ◽  
Ssr Markers ◽  
Bulked Segregant Analysis ◽  
Blast Resistance ◽  
Hot Spot ◽  
Resistance Breeding ◽  
Recurrent Parent ◽  
Simple Method ◽  
Multiple Alleles ◽  
Rice Landraces

Molecular markers tightly linked to target gene have been identified in different chromosomes to impose the genetic selection. This paper summarizes the progress and achievement made in breeding for blast resistance rice based on DNA markers. At least 40 genes conferring resistance to blast isolates with multiple alleles have been described. Both dominant and recessive resistance alleles have been found in many rice landraces. Highly polymorphic and easily detectable SSR markers are being used in breeding for blast resistance. Bulked segregant analysis (BSA) is the simple method for tagging resistance gene by SSR markers. Quantitative trait loci (QTLs) have also been mapped and most of them are linked to qualitative genes. Simple sequence repeat (SSR) markers linked to the gene are being used to select plants possessing the desired trait and markers throughout the genome are being used to select plants that are genetically similar to recurrent parent. Using SSR markers it may be possible to select blast resistance genotypes at any stage of crop development from any small part of crop, to conduct many round of selection, to select without inoculums, without scoring, and without testing in hot spot or artificial inoculation. Molecular based blast resistance breeding work is necessary to initiate in Nepal focusing on resistance gene tagging in Nepalese rice landraces and utilization.

scholarly journals A simple method to monitor hepatic gluconeogenesis and triglyceride synthesis following oral sugar tolerance test in obese adolescents

2019 ◽  
Vol 317 (1) ◽  
pp. R134-R142 ◽  
Author(s):  
Anne-Marie Carreau ◽  
Eunsook S. Jin ◽  
Yesenia Garcia-Reyes ◽  
Haseeb Rahat ◽  
Kristen J. Nadeau ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
De Novo ◽  
Tca Cycle ◽  
Tolerance Test ◽  
Serum Glucose ◽  
Pentose Phosphate ◽  
Invasive Technique ◽  
Simple Method ◽  
Obese Adolescents ◽  
Sugar Tolerance

Hepatic energy metabolism is a key element in many metabolic diseases. Hepatic anaplerosis provides carbons for gluconeogenesis (GNG) and triglyceride (TG) synthesis. We aimed to optimize a protocol that measures hepatic anaplerotic contribution for GNG, TG synthesis, and hepatic pentose phosphate pathway (PPP) activity using a single dose of oral [U−13C3]glycerol paired with an oral sugar tolerance test (OSTT) in a population with significant insulin resistance. The OSTT (75 g glucose + 25 g fructose) was administered to eight obese adolescents with polycystic ovarian syndrome (PCOS) followed by ingestion of [U-13C3]glycerol at t = 180 or t = 210 min. 13C-labeling patterns of serum glucose and TG-glycerol were determined by nuclear magnetic resonance. 13C enrichment in plasma TG-glycerol was detectable and stable from 240 to 390 min with the [U-13C3]glycerol drink at t = 180 min(3.65 ± 2.3 to 4.47 ± 1.4%; P > 0.4), but the enrichment was undetectable at 240 min with the glycerol drink at t = 210 min. The relative contribution from anaplerosis was determined at the end of the OSTT [18.5 ±3.4% ( t = 180 min) vs. 16.0 ± 3.5% ( t = 210 min); P = 0.27]. [U-13C3]glycerol was incorporated into GNG 390 min after the OSTT with an enrichment of 7.5–12.5%. Glucose derived from TCA cycle activity was 0.3–1%, and the PPP activity was 2.8–4.7%. In conclusion, it is possible to obtain relative measurements of hepatic anaplerotic contribution to both GNG and TG esterification following an OSTT in a highly insulin-resistant population using a minimally invasive technique. Tracer administration should be timed to allow enough de novo TG esterification and endogenous glucose release after the sugar drink.

scholarly journals A 2020 View on the Genetics of Developmental and Epileptic Encephalopathies

2020 ◽  
Vol 20 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Hannah C. Happ ◽  
Gemma L. Carvill
Keyword(s):  
Molecular Diagnosis ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Autosomal Recessive Inheritance ◽  
Small Subset ◽  
Recessive Inheritance ◽  
Epileptic Encephalopathies ◽  
Pathogenic Variants ◽  
Genetic Mosaicism ◽  
Genetic Landscape

Developmental and epileptic encephalopathies (DEEs) can be primarily attributed to genetic causes. The genetic landscape of DEEs has been largely shaped by the rise of high-throughput sequencing, which led to the discovery of new DEE-associated genes and helped identify de novo pathogenic variants. We discuss briefly the contribution of de novo variants to DEE and also focus on alternative inheritance models that contribute to DEE. First, autosomal recessive inheritance in outbred populations may have a larger contribution than previously appreciated, accounting for up to 13% of DEEs. A small subset of genes that typically harbor de novo variants have been associated with recessive inheritance, and often these individuals have more severe clinical presentations. Additionally, pathogenic variants in X-linked genes have been identified in both affected males and females, possibly due to a lack of X-chromosome inactivation skewing. Collectively, exome sequencing has resulted in a molecular diagnosis for many individuals with DEE, but this still leaves many cases unsolved. Multiple factors contribute to the missing etiology, including nonexonic variants, mosaicism, epigenetics, and oligogenic inheritance. Here, we focus on the first 2 factors. We discuss the promises and challenges of genome sequencing, which allows for a more comprehensive analysis of the genome, including interpretation of structural and noncoding variants and also yields a high number of de novo variants for interpretation. We also consider the contribution of genetic mosaicism, both what it means for a molecular diagnosis in mosaic individuals and the important implications for genetic counseling.

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