scholarly journals Phenotypic intrafamilial variability including H syndrome and Rosai Dorfman Disease associated with the same c.1088G>A mutation in the SLC29A3 gene.

2021 ◽  
Author(s):  
Hamza CHOUK ◽  
Mohamed BEN REJEB ◽  
Lobna BOUSSOFARA ◽  
Haïfa EL MABROUK ◽  
Najet GHARIANI ◽  
...  
Keyword(s):  
Family Members ◽  
Rare Event ◽  
Gene Mutations ◽  
Single Mutation ◽  
Nucleoside Transporter ◽  
Single Family ◽  
Rosai Dorfman Disease ◽  
The Face ◽  
Slc29a3 Gene ◽  
Tunisian Family

Abstract Background: Mutations in the SLC29A3 gene, which encodes the nucleoside transporter hENT3, has been implicated in syndromic forms of Histiocytosis including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, Faisalabad histiocytosis and Familial Rosai Dorfman disease (RDD). Herein, we report five new patients from a single family who present with phenotypes that associate features of H syndrome and Familial Rosai Dorfman Disease.Methods: We investigated the clinical, biochemical, histopathological and molecular findings in five Tunisian family Members' diagnosed as Familial RDD and/or H syndrome. The solute carrier family 29 (nucleoside transporters), member 3 ( SLC29A3 ) gene was screened for molecular diagnosis using direct Sanger sequencing.Results: Genetic analysis of all affected individuals revealed a previously reported missense mutation c.1088 G>A [p.Arg363Gln] in exon 6 of the SLC29A3 gene. Four affected members presented with clinical features consistent with classical H syndrome phenotype. While their cousin’s features were in keeping with the diagnosis of Familial Rosai Dorfman disease with a previously undescribed cutaneous RDD presenting as erythematous nodular plaques on the face. This report underlines the clinical variability of SLC29A3 disorders even with an identical mutation in the same family.Conclusion: We report a rare event of 5 Tunisian family Members' found to be homozygous for SLC29A3 gene mutations but showing a different phenotype severity. Our study reveals that despite a single mutation, the clinical expression of the SLC29A3 disorders may be significantly heterogeneous suggesting a poor genotype-phenotype correlation for the disease.

scholarly journals Phenotypic Intrafamilial Variability Including H Syndrome and Rosai Dorfman Disease Associated With the Same c.1088G>A mutation in the SLC29A3 gene.

2021 ◽  
Author(s):  
Hamza CHOUK ◽  
Mohamed BEN REJEB ◽  
Lobna BOUSSOFARA ◽  
Haïfa EL MABROUK ◽  
Najet GHARIANI ◽  
...  
Keyword(s):  
Family Members ◽  
Rare Event ◽  
Gene Mutations ◽  
Single Mutation ◽  
Nucleoside Transporter ◽  
Single Family ◽  
Rosai Dorfman Disease ◽  
The Face ◽  
Slc29a3 Gene ◽  
Tunisian Family

Abstract BackgroundMutations in the SLC29A3 gene, which encodes the nucleoside transporter hENT3, has been implicated in syndromic forms of Histiocytosis including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, Faisalabad histiocytosis and Familial Rosai Dorfman disease (RDD). Herein, we report five new patients from a single family who present with phenotypes that associate features of H syndrome and Familial Rosai Dorfman Disease.MethodsWe investigated the clinical, biochemical, histopathological and molecular findings in five Tunisian family Members' diagnosed with Familial RDD and/or H syndrome. The solute carrier family 29 (nucleoside transporters), member 3 (SLC29A3) gene was screened for molecular diagnosis using direct Sanger sequencing.ResultsGenetic analysis of all affected individuals revealed a previously reported missense mutation c.1088 G>A [p.Arg363Gln] in exon 6 of the SLC29A3 gene. Four affected members presented with clinical features consistent with the classical H syndrome phenotype. While their cousin’s features were in keeping with the diagnosis of Familial Rosai Dorfman disease with a previously undescribed cutaneous RDD presenting as erythematous nodular plaques on the face. This report underlines the clinical variability of SLC29A3 disorders even with an identical mutation in the same family.ConclusionWe report a rare event of 5 Tunisian family Members' found to be homozygous for SLC29A3 gene mutations but showing a different phenotype severity. Our study reveals that despite a single mutation, the clinical expression of the SLC29A3 disorders may be significantly heterogeneous suggesting a poor genotype-phenotype correlation for the disease.

scholarly journals Phenotypic intrafamilial variability including H syndrome and Rosai–Dorfman disease associated with the same c.1088G > A mutation in the SLC29A3 gene

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Hamza Chouk ◽  
Mohamed Ben Rejeb ◽  
Lobna Boussofara ◽  
Haїfa Elmabrouk ◽  
Najet Ghariani ◽  
...  
Keyword(s):  
Family Members ◽  
Rare Event ◽  
Gene Mutations ◽  
Disease Diagnosis ◽  
Single Mutation ◽  
Nucleoside Transporter ◽  
Single Family ◽  
Rosai Dorfman Disease ◽  
Slc29a3 Gene ◽  
Tunisian Family

Abstract Background Mutations in the SLC29A3 gene, which encodes the nucleoside transporter hENT3, have been implicated in syndromic forms of histiocytosis including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, Faisalabad histiocytosis and Familial Rosai–Dorfman disease (RDD). Herein, we report five new patients from a single family who present with phenotypes that associate features of H syndrome and Familial Rosai–Dorfman disease. Methods We investigated the clinical, biochemical, histopathological and molecular findings in five Tunisian family members' diagnosed with Familial RDD and/or H syndrome. The solute carrier family 29 (nucleoside transporters), member 3 (SLC29A3) gene was screened for molecular diagnosis using direct Sanger sequencing. Results Genetic analysis of all affected individuals revealed a previously reported missense mutation c.1088 G > A [p.Arg363Gln] in exon 6 of the SLC29A3 gene. Four affected members presented with clinical features consistent with the classical H syndrome phenotype. While their cousin’s features were in keeping with Familial Rosai–Dorfman disease diagnosis with a previously undescribed cutaneous RDD presenting as erythematous nodular plaques on the face. This report underlines the clinical variability of SLC29A3 disorders even with an identical mutation in the same family. Conclusion We report a rare event of 5 Tunisian family members' found to be homozygous for SLC29A3 gene mutations but showing a different phenotype severity. Our study reveals that despite a single mutation, the clinical expression of the SLC29A3 disorders may be significantly heterogeneous suggesting a poor genotype–phenotype correlation for the disease.

scholarly journals Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lu Cao ◽  
Ruixue Zhang ◽  
Liang Yong ◽  
Shirui Chen ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
Molecular Genetic ◽  
Family Members ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Mendelian Inheritance ◽  
Chinese Family ◽  
Multiple Sequence

Abstract Background Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Methods Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. Results A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. Conclusion Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.

scholarly journals Role of attitude in nurses’ responses to requests for assisted dying

2020 ◽  
pp. 096973302096677
Author(s):  
Michael Wilson ◽  
Marie Wilson ◽  
Suzanne Edwards ◽  
Lynette Cusack ◽  
Richard Wiechula
Keyword(s):  
Online Survey ◽  
Rare Event ◽  
Control Beliefs ◽  
Assisted Dying ◽  
Cross Sectional ◽  
Assisted Death ◽  
Institutional Ethics ◽  
The Face ◽  
Generalised Linear Modelling ◽  
And Control

Background: Legal assisted dying is a rare event, but as legalisation expands, requests for it will likely increase, and the nurse most often receives the informal, initial request. Objectives: To assess the effects of attitude in interaction with normative and control beliefs on an intention to respond to a request for legal assisted dying. Ethical considerations: The study had the lead author’s institutional ethics approval, and participants were informed that participation was both anonymous and voluntary. Methodology: This was a cross-sectional correlational study of 377 Australian registered nurses who completed an online survey. Generalised linear modelling assessed the effects of independent variables against intended responses to requests for legal assisted dying. Results: Compared to nurses who did not support legal assisted dying, nurses who did had stronger beliefs in patient rights, perceived social expectations to refer the request and stronger control in that intention. Nurses who did not support legal assisted dying had stronger beliefs in ethics of duty to the patient and often held dual intentions to discuss the request with the patient but also held an intention to deflect the request to consideration of alternatives. Discussion: This study advances the international literature by developing quantified models explaining the complexity of nurses’ experiences with requests for an assisted death. Attitude was operationalised in interaction with other beliefs and was identified as the strongest influence on intentions, but significantly moderated by ethical norms. Conclusion: The complex of determinants of those intentions to respond to requests for an assisted death suggests they are not isolated from each other. Nurses might have distinct intentions, but they can also hold multiple intentions even when they prioritise one. These findings present opportunities to prepare nurses in a way that enhances moral resilience in the face of complex moral encounters.

Reflections on 12 Years of Facilitating Alzheimer’s Caregiver Support Groups

2006 ◽  
Vol 7 (3) ◽  
pp. 135-140 ◽  
Author(s):  
Shirley S. Earle
Keyword(s):  
Support Groups ◽  
Progressive Disease ◽  
Family Members ◽  
Background Characteristics ◽  
Caregiver Support ◽  
The Face ◽  
Objective Being

This article discusses the background, characteristics, caregiver benefits, and facilitator rewards of Alzheimer’s Caregiver Support Groups conducted over a 12-year period. The objective being to motivate more professionals to start similar groups to increase supports for family members in the face of this devastating progressive disease and/or to encourage clients to consult their local Alzheimer’s Association to find caregiver groups already formed in or around their community. Providing or locating this service is strongly advocated by both the caregivers interviewed and the facilitator.

scholarly journals Glucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype–phenotype association throughout an activity distribution

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ying He ◽  
Yinhui Zhang ◽  
Xionghao Chen ◽  
Qiong Wang ◽  
Lifen Ling ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
G6pd Deficiency ◽  
National Level ◽  
Gene Mutations ◽  
Single Mutation ◽  
Missense Mutations ◽  
Severe Deficiency ◽  
Compound Mutation ◽  
Normal Males ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common hereditary disorder in China. The existing prevalence and molecular epidemiology of G6PD deficiency in China were geographically limited. In this study, the spectrum of G6PD gene mutations was well characterized in a large and diverse population all over the country; and the correlation of genotype and enzyme activity phenotype was explored for the first time. The results showed that the overall prevalence of G6PD deficiency in China was 2.10% at the national level. The top six common mutations were c.1388 G>A, c.1376 G>T, c.95 A>G, c.392 G>T, c.871 G>A and c.1024 C>T, accounting for more than 90% of G6PD deficient alleles. Compound mutation patterns were frequently observed in females with severe deficiency. The distribution of G6PD activities depended on the type of mutation patterns and genders. Hemizygote, homozygote, and compound heterozygote were predominantly associated with severe G6PD deficiency, whereas heterozygotes with single mutation mainly presented moderate enzyme deficiency. A significant gap between G6PD activities in hemizygous and normal males was observed, and yet, the overall distribution of that in females carrying missense mutations was a continuum from G6PD severely deficient to normal. This is the first report of discussing the association between G6PD genetic variants in the Chinese and enzyme activity phenotypes.

scholarly journals Equilibrative Nucleoside Transporter Family Members fromLeishmania donovaniAre Electrogenic Proton Symporters

2003 ◽  
Vol 278 (37) ◽  
pp. 35127-35134 ◽  
Author(s):  
Alex Stein ◽  
Gayatri Vaseduvan ◽  
Nicola S. Carter ◽  
Buddy Ullman ◽  
Scott M. Landfear ◽  
...  
Keyword(s):  
Family Members ◽  
Nucleoside Transporter ◽  
Equilibrative Nucleoside Transporter ◽  
Transporter Family

scholarly journals Current Progress on Equilibrative Nucleoside Transporter Function and Inhibitor Design

2019 ◽  
Vol 24 (10) ◽  
pp. 953-968 ◽  
Author(s):  
Shahid Rehan ◽  
Saman Shahid ◽  
Tiina A. Salminen ◽  
Veli-Pekka Jaakola ◽  
Ville O. Paavilainen
Keyword(s):  
Small Molecule ◽  
Family Members ◽  
Nucleoside Analogs ◽  
Homology Model ◽  
Nucleoside Transporters ◽  
Nucleoside Transporter ◽  
Surface Receptors ◽  
Cellular Import ◽  
Nucleoside Drugs ◽  
Small Molecule Modulators

Physiological nucleosides are used for the synthesis of DNA, RNA, and ATP in the cell and serve as universal mammalian signaling molecules that regulate physiological processes such as vasodilation and platelet aggregation by engaging with cell surface receptors. The same pathways that allow uptake of physiological nucleosides mediate the cellular import of synthetic nucleoside analogs used against cancer, HIV, and other viral diseases. Physiological nucleosides and nucleoside drugs are imported by two families of nucleoside transporters: the SLC28 concentrative nucleoside transporters (CNTs) and SLC29 equilibrative nucleoside transporters (ENTs). The four human ENT paralogs are expressed in distinct tissues, localize to different subcellular sites, and transport a variety of different molecules. Here we provide an overview of the known structure–function relationships of the ENT family with a focus on ligand binding and transport in the context of a new hENT1 homology model. We provide a generic residue numbering system for the different ENTs to facilitate the interpretation of mutational data produced using different ENT homologs. The discovery of paralog-selective small-molecule modulators is highly relevant for the design of new therapies and for uncovering the functions of poorly characterized ENT family members. Here, we discuss recent developments in the discovery of new paralog-selective small-molecule ENT inhibitors, including new natural product-inspired compounds. Recent progress in the ability to heterologously produce functional ENTs will allow us to gain insight into the structure and functions of different ENT family members as well as the rational discovery of highly selective inhibitors.

Clinical Charactistics of Ph-Negative MPN Patients with Coexistence of JAK2V617F, Calr and MPL Mutation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Dan Ma ◽  
Ping Liu ◽  
Chengyun Pan ◽  
Bingqing Cheng ◽  
Yaming Zhang ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Conflicts Of Interest ◽  
Gene Mutations ◽  
Interferon Α ◽  
Driver Gene ◽  
Fisher Exact Test ◽  
Single Mutation ◽  
Double Mutation ◽  
Mutation Carriers ◽  
Pubmed Database

Background and purpose: JAK2, CALR and MPL gene mutations are the driver genes leading to the pathogenesis of ph-negative myeloproliferative meoplasm (MPN). However, it's still unkonwn about the effect of double gene mutations coexisting in ph-negative MPN patients. In this study, we analyzed the clinical significance of the three driver gene mutations when they coexisted in patients with MPN. Methods: Collected bone marrow or peripheral blood samples of 221 patients with suspected MPN who were in the Affiliated Hospital of Guizhou Medical University between May 2017 and April 2020; qPCR detection for JAK2V617F mutation and sanger sequencing detection for CALR gene exon 9 and MPL Exon 10 mutation. Searched Pubmed database related to the coexistence of the three driver gene mutations and extracted information; Fisher exact test to analyze the differences in clinical characteristics between double mutation carriers and single mutation carriers. Shapiro-Wilk statistical analysis of the differences in clinical characteristics of ET patients with different types of double mutations. Results: 1 ET and 1 PMF patient carried both JAK2V617F and CALR gene mutations were found in our center, accounting for 0.9% of ph-negative MPN. The CALR carried by PMF patients was a newly discovered mutation type, c.1126_1127insTTTGC, R376Lfs*56. Through database search, we collected 26 literatures involving MPN case reports with double-driver gene mutations. By fitting analysis with the clinical information of positive patients in our center, a total of 74 MPN patients were collected, of which the number of ET patients was the largest(57/74, accounting for 77.03%). The most common coexisting mutant type was JAK2V617F plus CALR (63/74, 85.14%). The age of onset of MPN patients with double-driver gene mutations was significantly higher than that of single-mutation carriers, and the proportion of patients over 70 years of age was higher (p<0.05), and double mutation carriers had higher platelet count levels(Plt) (p<0.05). The proportion of patients with splenomegalia was lower (p<0.05). The clinical characteristics of ET patients were similar to MPN patients, but no difference in the incidence of splenomegalia (p>0.05). Among PMF patients, the Plt and the proportion of patients with megasplenomegaly in double mutation carriers were similar to those in MPN patients, but the hemoglobin(Hb) was higher (p<0.05). In addition, we also compared the clinical characteristics of ET patients with different gene mutation types. The results showed that the Hb of patients with JAK2V617F and CALR mutations were higher than those of ET patients with JAK2V617F and MPL mutations (p<0.05), but the Plt level is low (p<0.05). Although there were no significant differences in age, gender, IPSET-thrombosis and IPSET (IWG-MRT) scores and WBC between the two groups, the proportion of female ET patients with JAKV617F with MPL mutation was significantly higher than that of JAK2V617F with CALR mutation group (p<0.05). And the proportion of patients with WBC exceeding 11×109/L was also higher (p<0.05). In addition, only one PV patient carried JAK2V617F and CALR, and achieved partial or complete remission after treatment with standard treatment regimens (hydroxyurea or interferon-α). Conclusion: JAK2V617F, CALR and MPL gene mutations are not mutually exclusive in MPN patients, but a certain number of double mutation carriers are ignored. Compared with patients with single-gene mutations, patients with double-gene mutations are older and have higher platelet counts, and should be treated differently in later treatment. At the same time, there are also differences between ET patients with different mutation combinations. These results suggest that it is very necessary for MPN patients to check for three driver gene mutations at the same time, and this type of patients may become a new subtype of MPN. Disclosures No relevant conflicts of interest to declare.

IDH1 and IDH2 mutations are Not Frequent In Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4992-4992 ◽  
Author(s):  
Christian Langer ◽  
Mariam Ibañez ◽  
Peter Liebisch ◽  
Thorsten Zenz ◽  
Stefan Knop ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Performance ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Rare Event ◽  
Gene Mutations ◽  
Isocitrate Dehydrogenase 1 ◽  
Aberrant Expression ◽  
Genetic Abnormalities ◽  
Idh1 And Idh2 Mutations

Abstract Abstract 4992 Multiple myeloma (MM) is characterized by frequent and complex genomic abnormalities. However, most genetic abnormalities are already present in the precursor state of MM, the monoclonal gammopathy of undetermined significance (MGUS). Therefore, it is likely that secondary genetic events might contribute to the development from MGUS to symptomatic MM. Mutations in isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) genes have recently been described as relatively frequent molecular lesions in gliomas and in acute myeloid leukemia (AML). However no larger study has so far examined the frequency of IDH1 and IDH2 gene mutations in patients (pts) with MM. Methods: In 188 pts with MM genomic DNA from CD138 sorted plasma cells was used for analyses. Exon 4 of both IDH1 and IDH2 were amplified by PCR and the amplicons were analyzed using a combination of denaturing high-performance liquid chromatography and DNA sequencing. All patients were also characterized by a comprehensive set of FISH probes for the presence of recurring cytogenetic abnormalities. Results: 185 out of 188 samples were evaluable for analyses. One missense mutation in the IDH2 gene (c.G419A) was identified in the cohort of 185 MM pts (0.5%). This mutation was described as the most frequent IDH2 mutation in AML and is predicted to cause an amino acid change from arginine to glutamin at position 140 (p.R140Q). On cytogenetic analysis this patient harbored a translocation t(11;14) resulting in aberrant expression of CCND1. Additionally, in 15 pts (8%) the recently described single nucleotide polymorphism (SNP) in the IDH1 gene (rs11554137) was detected that has been reported as an adverse prognostic factor in cytogenetically normal AML. Summary: Mutations in the IDH1/2 genes are a rare event in MM (0.5%). Further studies are warranted to address the issue if IDH1/2 mutations are restricted to distinct genetic subgroups as for example the group of MM pts with translocation t(11;14). Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document