Background Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating mov... more Background Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating movement disorders. The etiopathogenesis is complex, both genetic and environmental factors playing a role, but remains elusive. The CACNA1B gene codes for the N-type neuronal voltage-gated calcium channels CaV2.2, which may play a role in the development of some IFD. Methods We analyzed samples from the GENDYS cohort for mutations in CACNA1B gene, using targeted next-generation sequencing (NGS). Results The GENDYS cohort consists of 120 people with adult-onset IFD (cervical dystonia 47.5%, blepharospasm 47.2%, others 8.3%). Of these, 35% had subsequent topographical extension. Average age at onset was 42 and average disease durations 8 years. Targeted NGS revealed a novel frameshift mutation c.2291AGG > A, in exon 19, and a previously reported variant, c.6834T > G, in exon 47. Conclusion Our findings suggest that disease-causing mutations in CACNA1B gene may be involved in the development of some adult-onset IFD. To our knowledge, this is the first study that identified a disease-causing CACNA1B gene mutation in association with adult-onset IFD.
Background: As a major crossroads between Asia and Europe, Romania has experienced continuous mig... more Background: As a major crossroads between Asia and Europe, Romania has experienced continuous migration and invasion episodes. The precise routes may have been shaped by the topology of the territory and had diverse impacts on the genetic structure of mitochondrial DNA (mtDNA) in historical Romanian provinces. We studied 714 Romanians from all historical provinces, Wallachia, Dobrudja, Moldavia, and Transylvania, by analyzing the mtDNA control region and coding markers to encompass the complete landscape of mtDNA haplogroups. Results: We observed a homogenous distribution of the majority of haplogroups among the Romanian provinces and a clear association with the European populations. A principal component analysis and multidimensional scaling analysis supported the genetic similarity of the Wallachia, Moldavia, and Dobrudja groups with the Balkans, while the Transylvania population was closely related to Central European groups. These findings could be explained by the topology of the Romanian territory, where the Carpathian Arch played an important role in migration patterns. Signals of Asian maternal lineages were observed in all Romanian historical provinces, indicating gene flow along the migration routes through East Asia and Europe. Conclusions: Our current findings based on the mtDNA analysis of populations in historical provinces of Romania suggest similarity between populations in Transylvania and Central Europe, supported both by the observed clines in haplogroup frequencies for several European and Asian maternal lineages and MDS analyses.
Fibroza chistică, numită și mucoviscidoză, este cea mai frecventă boală pulmonară ereditară și es... more Fibroza chistică, numită și mucoviscidoză, este cea mai frecventă boală pulmonară ereditară și este produsă de mutații în gena CFTR, ce codifică un canal anionic pentru clor și bicarbonat cu rol în reglarea metabolismului bicarbonatului și sării. În momentul de față, aproximativ jumătate din totalul pacienților cu fibroză chistică pot beneficia de terapie personalizată cu ajutorul modulatorilor, substanțe care restaurează sau îmbunătățesc funcționalitatea și stabilitatea CFTR. Mai mult, la ora actuală se află în stadiul de studiu clinic și alte tipuri de terapii, ca de exemplu terapia genică utilizând sistemul CRISP/CAS-9, oligonucleotide antisens modificate sau inserția genei sălbatice utilizând particule nanolipidice sau vectori virali. Acest articol își propune să treacă în revistă principalele tipuri de terapii aprobate sau aflate în stadiul de studiu clinic pentru tratamentul fibrozei chistice.
Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia wit... more Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia with focal onset (IDFO), but their pathophysiological relationship is not clear. We aimed to identify the prevalence of depression and neurocognitive impairment in a group of patients with idiopathic dystonia with focal onset and their impact on the patients' quality of life. This study represents a component of an ongoing research project-GENDYS. From the database of this project, we selected 48 patients 56.62+/-14.16 years old who have been examined clinically and using specific scales: Patient Health Questionnaire-9 (for depression), Montreal Cognitive Assessment-MoCA (for cognitive impairment), and a 5-degree analog scale for subjective perception of the severity of the disease. We conducted a descriptive cross-sectional study on patients with depression and cognition evaluated by the above-mentioned scales. We also performed a nested case-control analysis on 20 IDFO patients with and without at least moderate depression matched for age and gender; the cutoffs for depression were PHQ-9 score ≥10 and PHQ9 <5, for the depression group and the control group, respectively. The cutoff for MoCA was 26 points. 22 IDFO patients (46%) had depression; 54.5% of IDFO patients with depression had cognitive impairment, indicating a slight trend of increased cognitive impairment in those with depression compared to those without; the perception of the severity of disease was the greatest in patients with depression. Depression is more prevalent in patients with IDFO and is associated with a worse perception of the disease severity.
Background: Tuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last... more Background: Tuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last years, resistant strains of the etiological agent, Mycobacterium tuberculosis, have emerged, thus demanding more triage tests to identify active pulmonary TB (PTB) patients and to evaluate their disease severity. Therefore, acute-phase reaction serum tests are required f or monito ring T B p atients, amon g WHO s ymp tom screenin g recommendations. C-reactive protein (CRP) is a non-specific inflammatory biomarker that has been recently proposed for TB screening and can be quantitatively analyzed through cost-effective point-of-care assays. A previous meta-analysis found CRP to be highly sensitive and moderately specific for active PTB with confirmed HIV infection. Methods: We performed a meta-analysis update of diagnostic tests, pooling sensitivities, and specificities in order to assess the accuracy of CRP as a potential test for the screening of HIV-associated PTB in outpatients. We searched MEDLINE, Web of Science, and SCOPUS for eligible articles before 19 October 2021. Results: We identified 13 eligible studies with HIV-positive patients with PTB. At a CRP threshold of 10 mg/L, CRP pooled sensitivity was 87% (76%-93%) and pooled specificity was 67% (49%-81%), with an area under the curve (AUC) of 0.858. Using a CRP threshold of 8 mg/L, pooled sensitivity was 82% (72%-89%) and pooled specificity was 82% (67%-92%), with an AUC of 0.879. We found Frontiers in Immunology frontiersin.org 01
Cystic fibrosis, also named mucoviscidosis, is the most frequent hereditary pulmonary disease and... more Cystic fibrosis, also named mucoviscidosis, is the most frequent hereditary pulmonary disease and is produced by mutations in the CFTR gene, encoding an anionic channel for chloride and bicarbonate involved in the regulation of salt and bicarbonate metabolisms. Currently, about half of the patients with cystic fibrosis can benefit personalized therapy consisting in modulators, drugs which restore or improve the functionality and stability of CFTR. Moreover, presently, other therapies, such as gene therapy using the CRISP/CAS-9, modified antisense oligonucleotides or the insertion of the wild-type gene using nanolipidic particles or viral vectors, are being developed. This article aims to take stock of the principal types of cystic fibrosis therapies which have been approved or are in clinical trials.
Deletions of the Y chromosome are a significant cause of spermatogenic failure. Three major delet... more Deletions of the Y chromosome are a significant cause of spermatogenic failure. Three major deletion intervals have been defined and termed AZFa, AZFb and AZFc. Here, we report an unusual case of a proximal AZFb deletion that includes the Y chromosome palindromic sequence P4 and a novel heat shock factor (HSFY). This deletion neither include the genes EIF1AY, RPS4Y2 nor copies of the RBMY1 genes. The individual presented with idiopathic azoospermia. We propose that deletions of the testis-specific HSFY gene family may be a cause of unexplained cases of idiopathic male infertility. This deletion would not have been detected using current protocols for Y chromosome microdeletion screens, therefore we recommend that current screening protocols be extended to include this region and other palindrome sequences that contain genes expressed specifically in the testis.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B ge... more Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson's disease ever reported of 1:1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (1861 years) showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson's disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson's disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
BackgroundTuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last y... more BackgroundTuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last years, resistant strains of the etiological agent, Mycobacterium tuberculosis, have emerged, thus demanding more triage tests to identify active pulmonary TB (PTB) patients and to evaluate their disease severity. Therefore, acute-phase reaction serum tests are required for monitoring TB patients, among WHO symptom screening recommendations. C-reactive protein (CRP) is a non-specific inflammatory biomarker that has been recently proposed for TB screening and can be quantitatively analyzed through cost-effective point-of-care assays. A previous meta-analysis found CRP to be highly sensitive and moderately specific for active PTB with confirmed HIV infection.MethodsWe performed a meta-analysis update of diagnostic tests, pooling sensitivities, and specificities in order to assess the accuracy of CRP as a potential test for the screening of HIV-associated PTB in outpatients. We searched MEDLI...
Pro-inflammatory mediators play an important role in the pathogenesis of pulmonary tuberculosis. ... more Pro-inflammatory mediators play an important role in the pathogenesis of pulmonary tuberculosis. Consecutively, 26 pulmonary tuberculosis patients were enrolled in our study based on the exclusion criteria. We have used Spearman’s correlation analysis, hierarchical clustering and regression modelling to evaluate the association of 11 biomarkers with culture status after antituberculosis treatment. The results of our study demonstrated that six inflammatory biomarkers of 11, C-reactive protein (CRP), white blood cells (WBC), neutrophils, interferon gamma inducible protein 10, C-reactive protein (CRP) to albumin ratio (CAR) and neutrophil to albumin ratio (NAR), were significantly associated with culture negativity. The predictive ability of a composite model of seven biomarkers was superior to that of any single biomarker based on area under the receiver operating characteristic curve (AUC) analysis, indicating an excellent prediction efficacy (AUC:0.892; 95% CI:0.732-1.0). We also f...
Our study objective was to construct models using 20 routine laboratory parameters on admission t... more Our study objective was to construct models using 20 routine laboratory parameters on admission to predict disease severity and mortality risk in a group of 254 hospitalized COVID-19 patients. Considering the influence of confounding factors in this single-center study, we also retrospectively assessed the correlations between the risk of death and the routine laboratory parameters within individual comorbidity subgroups. In multivariate regression models and by ROC curve analysis, a model of three routine laboratory parameters (AUC 0.85; 95% CI: 0.79–0.91) and a model of six laboratory factors (AUC 0.86; 95% CI: 0.81–0.91) were able to predict severity and mortality of COVID-19, respectively, compared with any other individual parameter. Hierarchical cluster analysis showed that inflammatory laboratory markers grouped together in three distinct clusters including positive correlations: WBC with NEU, NEU with neutrophil-to-lymphocyte ratio (NLR), NEU with systemic immune-inflammatio...
Joubert syndrome is a genetic disease with an autosomal-recessive or X-linked inheritance pattern... more Joubert syndrome is a genetic disease with an autosomal-recessive or X-linked inheritance pattern caused by pathogenic variants in at least 35 genes, all encoding structures of the primary cilium involved in signaling pathways that coordinate the normal development of the kidneys, retina, brain, liver and skeletal system. The symptoms can consist in cystic renal disease and renal dystrophy, oculomotor apraxia, global developmental delay, hypotonia evolving into ataxia, skeletal and endocrine abnormalities, abnormal breathing patterns and congenital hepatic fibrosis, with the neurologic and ophthalmologic manifestations appearing early in life. The diagnostic hallmark is “the molar tooth sign”, a malformation of the brainstem and cerebellum easily identifiable using brain imaging techniques. As Joubert syndrome is a highly heterogeneous disease with a large type of phenotypes, it is oftentimes underdiagnosed. This article presents a case of Joubert syndrome type 17, a rare syndrome w...
19q13 microdeletion syndrome is a very rare genetic disease characterized by pre- and postnatal g... more 19q13 microdeletion syndrome is a very rare genetic disease characterized by pre- and postnatal growth retardation, intellectual disability, expressive language impairment, ectodermal dysplasia, and slender habitus. Since the description of the first case in 1998, less than 30 cases have been reported worldwide. This article aims to review the knowledge gathered so far on this subject and to present the case of a 10-year-old girl admitted to the National University Center for Children Neurorehabilitation “Dr. Nicolae Robanescu” in November of 2018 who presented a slender habitus, growth retardation, facial dysmorphism, skeletal abnormalities, and ectodermal dysplasia. Array-CGH analysis revealed a 1.53 Mb deletion in the 19q13.32-q13.33 region. MLPA for the FKRP gene revealed that the microdeletion was de novo. The patient’s phenotype overlapped with the clinical features of 19q13 microdeletion syndrome. To our knowledge, this is the first case of 19q13 microdeletion syndrome to eve...
Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia wit... more Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia with focal onset (IDFO), but their pathophysiological relationship is not clear. We aimed to identify the prevalence of depression and neurocognitive impairment in a group of patients with idiopathic dystonia with focal onset and their impact on the patients’ quality of life. This study represents a component of an ongoing research project – GENDYS. From the database of this project, we selected 48 patients 56.62+/-14.16 years old who have been examined clinically and using specific scales: Patient Health Questionnaire-9 (for depression), Montreal Cognitive Assessment - MoCA (for cognitive impairment), and a 5-degree analog scale for subjective perception of the severity of the disease. We conducted a descriptive cross-sectional study on patients with depression and cognition evaluated by the above-mentioned scales. We also performed a nested case-control analysis on 20 IDFO patients with a...
Cystic fibrosis, also named mucoviscidosis, is the most frequent hereditary pulmonary disease and... more Cystic fibrosis, also named mucoviscidosis, is the most frequent hereditary pulmonary disease and is produced by mutations in the CFTR gene, encoding an anionic channel for chloride and bicarbonate involved in the regulation of salt and bicarbonate metabolisms. Currently, about half of the patients with cystic fibrosis can benefit personalized therapy consisting in modulators, drugs which restore or improve the functionality and stability of CFTR. Moreover, presently, other therapies, such as gene therapy using the CRISP/CAS-9, modified antisense oligonucleotides or the insertion of the wild-type gene using nanolipidic particles or viral vectors, are being developed. This article aims to take stock of the principal types of cystic fibrosis therapies which have been approved or are in clinical trials.
Background Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating mov... more Background Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating movement disorders. The etiopathogenesis is complex, both genetic and environmental factors playing a role, but remains elusive. The CACNA1B gene codes for the N-type neuronal voltage-gated calcium channels CaV2.2, which may play a role in the development of some IFD. Methods We analyzed samples from the GENDYS cohort for mutations in CACNA1B gene, using targeted next-generation sequencing (NGS). Results The GENDYS cohort consists of 120 people with adult-onset IFD (cervical dystonia 47.5%, blepharospasm 47.2%, others 8.3%). Of these, 35% had subsequent topographical extension. Average age at onset was 42 and average disease durations 8 years. Targeted NGS revealed a novel frameshift mutation c.2291AGG > A, in exon 19, and a previously reported variant, c.6834T > G, in exon 47. Conclusion Our findings suggest that disease-causing mutations in CACNA1B gene may be involved in the develo...
Background Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating mov... more Background Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating movement disorders. The etiopathogenesis is complex, both genetic and environmental factors playing a role, but remains elusive. The CACNA1B gene codes for the N-type neuronal voltage-gated calcium channels CaV2.2, which may play a role in the development of some IFD. Methods We analyzed samples from the GENDYS cohort for mutations in CACNA1B gene, using targeted next-generation sequencing (NGS). Results The GENDYS cohort consists of 120 people with adult-onset IFD (cervical dystonia 47.5%, blepharospasm 47.2%, others 8.3%). Of these, 35% had subsequent topographical extension. Average age at onset was 42 and average disease durations 8 years. Targeted NGS revealed a novel frameshift mutation c.2291AGG > A, in exon 19, and a previously reported variant, c.6834T > G, in exon 47. Conclusion Our findings suggest that disease-causing mutations in CACNA1B gene may be involved in the development of some adult-onset IFD. To our knowledge, this is the first study that identified a disease-causing CACNA1B gene mutation in association with adult-onset IFD.
Background: As a major crossroads between Asia and Europe, Romania has experienced continuous mig... more Background: As a major crossroads between Asia and Europe, Romania has experienced continuous migration and invasion episodes. The precise routes may have been shaped by the topology of the territory and had diverse impacts on the genetic structure of mitochondrial DNA (mtDNA) in historical Romanian provinces. We studied 714 Romanians from all historical provinces, Wallachia, Dobrudja, Moldavia, and Transylvania, by analyzing the mtDNA control region and coding markers to encompass the complete landscape of mtDNA haplogroups. Results: We observed a homogenous distribution of the majority of haplogroups among the Romanian provinces and a clear association with the European populations. A principal component analysis and multidimensional scaling analysis supported the genetic similarity of the Wallachia, Moldavia, and Dobrudja groups with the Balkans, while the Transylvania population was closely related to Central European groups. These findings could be explained by the topology of the Romanian territory, where the Carpathian Arch played an important role in migration patterns. Signals of Asian maternal lineages were observed in all Romanian historical provinces, indicating gene flow along the migration routes through East Asia and Europe. Conclusions: Our current findings based on the mtDNA analysis of populations in historical provinces of Romania suggest similarity between populations in Transylvania and Central Europe, supported both by the observed clines in haplogroup frequencies for several European and Asian maternal lineages and MDS analyses.
Fibroza chistică, numită și mucoviscidoză, este cea mai frecventă boală pulmonară ereditară și es... more Fibroza chistică, numită și mucoviscidoză, este cea mai frecventă boală pulmonară ereditară și este produsă de mutații în gena CFTR, ce codifică un canal anionic pentru clor și bicarbonat cu rol în reglarea metabolismului bicarbonatului și sării. În momentul de față, aproximativ jumătate din totalul pacienților cu fibroză chistică pot beneficia de terapie personalizată cu ajutorul modulatorilor, substanțe care restaurează sau îmbunătățesc funcționalitatea și stabilitatea CFTR. Mai mult, la ora actuală se află în stadiul de studiu clinic și alte tipuri de terapii, ca de exemplu terapia genică utilizând sistemul CRISP/CAS-9, oligonucleotide antisens modificate sau inserția genei sălbatice utilizând particule nanolipidice sau vectori virali. Acest articol își propune să treacă în revistă principalele tipuri de terapii aprobate sau aflate în stadiul de studiu clinic pentru tratamentul fibrozei chistice.
Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia wit... more Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia with focal onset (IDFO), but their pathophysiological relationship is not clear. We aimed to identify the prevalence of depression and neurocognitive impairment in a group of patients with idiopathic dystonia with focal onset and their impact on the patients' quality of life. This study represents a component of an ongoing research project-GENDYS. From the database of this project, we selected 48 patients 56.62+/-14.16 years old who have been examined clinically and using specific scales: Patient Health Questionnaire-9 (for depression), Montreal Cognitive Assessment-MoCA (for cognitive impairment), and a 5-degree analog scale for subjective perception of the severity of the disease. We conducted a descriptive cross-sectional study on patients with depression and cognition evaluated by the above-mentioned scales. We also performed a nested case-control analysis on 20 IDFO patients with and without at least moderate depression matched for age and gender; the cutoffs for depression were PHQ-9 score ≥10 and PHQ9 <5, for the depression group and the control group, respectively. The cutoff for MoCA was 26 points. 22 IDFO patients (46%) had depression; 54.5% of IDFO patients with depression had cognitive impairment, indicating a slight trend of increased cognitive impairment in those with depression compared to those without; the perception of the severity of disease was the greatest in patients with depression. Depression is more prevalent in patients with IDFO and is associated with a worse perception of the disease severity.
Background: Tuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last... more Background: Tuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last years, resistant strains of the etiological agent, Mycobacterium tuberculosis, have emerged, thus demanding more triage tests to identify active pulmonary TB (PTB) patients and to evaluate their disease severity. Therefore, acute-phase reaction serum tests are required f or monito ring T B p atients, amon g WHO s ymp tom screenin g recommendations. C-reactive protein (CRP) is a non-specific inflammatory biomarker that has been recently proposed for TB screening and can be quantitatively analyzed through cost-effective point-of-care assays. A previous meta-analysis found CRP to be highly sensitive and moderately specific for active PTB with confirmed HIV infection. Methods: We performed a meta-analysis update of diagnostic tests, pooling sensitivities, and specificities in order to assess the accuracy of CRP as a potential test for the screening of HIV-associated PTB in outpatients. We searched MEDLINE, Web of Science, and SCOPUS for eligible articles before 19 October 2021. Results: We identified 13 eligible studies with HIV-positive patients with PTB. At a CRP threshold of 10 mg/L, CRP pooled sensitivity was 87% (76%-93%) and pooled specificity was 67% (49%-81%), with an area under the curve (AUC) of 0.858. Using a CRP threshold of 8 mg/L, pooled sensitivity was 82% (72%-89%) and pooled specificity was 82% (67%-92%), with an AUC of 0.879. We found Frontiers in Immunology frontiersin.org 01
Cystic fibrosis, also named mucoviscidosis, is the most frequent hereditary pulmonary disease and... more Cystic fibrosis, also named mucoviscidosis, is the most frequent hereditary pulmonary disease and is produced by mutations in the CFTR gene, encoding an anionic channel for chloride and bicarbonate involved in the regulation of salt and bicarbonate metabolisms. Currently, about half of the patients with cystic fibrosis can benefit personalized therapy consisting in modulators, drugs which restore or improve the functionality and stability of CFTR. Moreover, presently, other therapies, such as gene therapy using the CRISP/CAS-9, modified antisense oligonucleotides or the insertion of the wild-type gene using nanolipidic particles or viral vectors, are being developed. This article aims to take stock of the principal types of cystic fibrosis therapies which have been approved or are in clinical trials.
Deletions of the Y chromosome are a significant cause of spermatogenic failure. Three major delet... more Deletions of the Y chromosome are a significant cause of spermatogenic failure. Three major deletion intervals have been defined and termed AZFa, AZFb and AZFc. Here, we report an unusual case of a proximal AZFb deletion that includes the Y chromosome palindromic sequence P4 and a novel heat shock factor (HSFY). This deletion neither include the genes EIF1AY, RPS4Y2 nor copies of the RBMY1 genes. The individual presented with idiopathic azoospermia. We propose that deletions of the testis-specific HSFY gene family may be a cause of unexplained cases of idiopathic male infertility. This deletion would not have been detected using current protocols for Y chromosome microdeletion screens, therefore we recommend that current screening protocols be extended to include this region and other palindrome sequences that contain genes expressed specifically in the testis.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B ge... more Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson's disease ever reported of 1:1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (1861 years) showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson's disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson's disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
BackgroundTuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last y... more BackgroundTuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last years, resistant strains of the etiological agent, Mycobacterium tuberculosis, have emerged, thus demanding more triage tests to identify active pulmonary TB (PTB) patients and to evaluate their disease severity. Therefore, acute-phase reaction serum tests are required for monitoring TB patients, among WHO symptom screening recommendations. C-reactive protein (CRP) is a non-specific inflammatory biomarker that has been recently proposed for TB screening and can be quantitatively analyzed through cost-effective point-of-care assays. A previous meta-analysis found CRP to be highly sensitive and moderately specific for active PTB with confirmed HIV infection.MethodsWe performed a meta-analysis update of diagnostic tests, pooling sensitivities, and specificities in order to assess the accuracy of CRP as a potential test for the screening of HIV-associated PTB in outpatients. We searched MEDLI...
Pro-inflammatory mediators play an important role in the pathogenesis of pulmonary tuberculosis. ... more Pro-inflammatory mediators play an important role in the pathogenesis of pulmonary tuberculosis. Consecutively, 26 pulmonary tuberculosis patients were enrolled in our study based on the exclusion criteria. We have used Spearman’s correlation analysis, hierarchical clustering and regression modelling to evaluate the association of 11 biomarkers with culture status after antituberculosis treatment. The results of our study demonstrated that six inflammatory biomarkers of 11, C-reactive protein (CRP), white blood cells (WBC), neutrophils, interferon gamma inducible protein 10, C-reactive protein (CRP) to albumin ratio (CAR) and neutrophil to albumin ratio (NAR), were significantly associated with culture negativity. The predictive ability of a composite model of seven biomarkers was superior to that of any single biomarker based on area under the receiver operating characteristic curve (AUC) analysis, indicating an excellent prediction efficacy (AUC:0.892; 95% CI:0.732-1.0). We also f...
Our study objective was to construct models using 20 routine laboratory parameters on admission t... more Our study objective was to construct models using 20 routine laboratory parameters on admission to predict disease severity and mortality risk in a group of 254 hospitalized COVID-19 patients. Considering the influence of confounding factors in this single-center study, we also retrospectively assessed the correlations between the risk of death and the routine laboratory parameters within individual comorbidity subgroups. In multivariate regression models and by ROC curve analysis, a model of three routine laboratory parameters (AUC 0.85; 95% CI: 0.79–0.91) and a model of six laboratory factors (AUC 0.86; 95% CI: 0.81–0.91) were able to predict severity and mortality of COVID-19, respectively, compared with any other individual parameter. Hierarchical cluster analysis showed that inflammatory laboratory markers grouped together in three distinct clusters including positive correlations: WBC with NEU, NEU with neutrophil-to-lymphocyte ratio (NLR), NEU with systemic immune-inflammatio...
Joubert syndrome is a genetic disease with an autosomal-recessive or X-linked inheritance pattern... more Joubert syndrome is a genetic disease with an autosomal-recessive or X-linked inheritance pattern caused by pathogenic variants in at least 35 genes, all encoding structures of the primary cilium involved in signaling pathways that coordinate the normal development of the kidneys, retina, brain, liver and skeletal system. The symptoms can consist in cystic renal disease and renal dystrophy, oculomotor apraxia, global developmental delay, hypotonia evolving into ataxia, skeletal and endocrine abnormalities, abnormal breathing patterns and congenital hepatic fibrosis, with the neurologic and ophthalmologic manifestations appearing early in life. The diagnostic hallmark is “the molar tooth sign”, a malformation of the brainstem and cerebellum easily identifiable using brain imaging techniques. As Joubert syndrome is a highly heterogeneous disease with a large type of phenotypes, it is oftentimes underdiagnosed. This article presents a case of Joubert syndrome type 17, a rare syndrome w...
19q13 microdeletion syndrome is a very rare genetic disease characterized by pre- and postnatal g... more 19q13 microdeletion syndrome is a very rare genetic disease characterized by pre- and postnatal growth retardation, intellectual disability, expressive language impairment, ectodermal dysplasia, and slender habitus. Since the description of the first case in 1998, less than 30 cases have been reported worldwide. This article aims to review the knowledge gathered so far on this subject and to present the case of a 10-year-old girl admitted to the National University Center for Children Neurorehabilitation “Dr. Nicolae Robanescu” in November of 2018 who presented a slender habitus, growth retardation, facial dysmorphism, skeletal abnormalities, and ectodermal dysplasia. Array-CGH analysis revealed a 1.53 Mb deletion in the 19q13.32-q13.33 region. MLPA for the FKRP gene revealed that the microdeletion was de novo. The patient’s phenotype overlapped with the clinical features of 19q13 microdeletion syndrome. To our knowledge, this is the first case of 19q13 microdeletion syndrome to eve...
Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia wit... more Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia with focal onset (IDFO), but their pathophysiological relationship is not clear. We aimed to identify the prevalence of depression and neurocognitive impairment in a group of patients with idiopathic dystonia with focal onset and their impact on the patients’ quality of life. This study represents a component of an ongoing research project – GENDYS. From the database of this project, we selected 48 patients 56.62+/-14.16 years old who have been examined clinically and using specific scales: Patient Health Questionnaire-9 (for depression), Montreal Cognitive Assessment - MoCA (for cognitive impairment), and a 5-degree analog scale for subjective perception of the severity of the disease. We conducted a descriptive cross-sectional study on patients with depression and cognition evaluated by the above-mentioned scales. We also performed a nested case-control analysis on 20 IDFO patients with a...
Cystic fibrosis, also named mucoviscidosis, is the most frequent hereditary pulmonary disease and... more Cystic fibrosis, also named mucoviscidosis, is the most frequent hereditary pulmonary disease and is produced by mutations in the CFTR gene, encoding an anionic channel for chloride and bicarbonate involved in the regulation of salt and bicarbonate metabolisms. Currently, about half of the patients with cystic fibrosis can benefit personalized therapy consisting in modulators, drugs which restore or improve the functionality and stability of CFTR. Moreover, presently, other therapies, such as gene therapy using the CRISP/CAS-9, modified antisense oligonucleotides or the insertion of the wild-type gene using nanolipidic particles or viral vectors, are being developed. This article aims to take stock of the principal types of cystic fibrosis therapies which have been approved or are in clinical trials.
Background Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating mov... more Background Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating movement disorders. The etiopathogenesis is complex, both genetic and environmental factors playing a role, but remains elusive. The CACNA1B gene codes for the N-type neuronal voltage-gated calcium channels CaV2.2, which may play a role in the development of some IFD. Methods We analyzed samples from the GENDYS cohort for mutations in CACNA1B gene, using targeted next-generation sequencing (NGS). Results The GENDYS cohort consists of 120 people with adult-onset IFD (cervical dystonia 47.5%, blepharospasm 47.2%, others 8.3%). Of these, 35% had subsequent topographical extension. Average age at onset was 42 and average disease durations 8 years. Targeted NGS revealed a novel frameshift mutation c.2291AGG > A, in exon 19, and a previously reported variant, c.6834T > G, in exon 47. Conclusion Our findings suggest that disease-causing mutations in CACNA1B gene may be involved in the develo...
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