The most common founder pathogenic variant c.868G > A (p.Val290Met) in the NPHS2 gene in a representative adult Czech cohort with focal segmental glomerulosclerosis is associated with a milder disease and its underdiagnosis in childhood

BackgroundGenetic focal segmental glomerulosclerosis (FSGS) is caused by pathogenic variants in a broad spectrum of genes that have a variable representation based on subjects' ethnicity and/or age. The most frequently mutated autosomal recessive gene in FSGS is NPHS2. In this study, we analyzed the spectrum of NPHS2 variants and their associated phenotype in Czech adult FSGS patients.MethodsA representative cohort of 234 adult patients with FSGS, derived from 225 families originating from all regions of Czechia, was analyzed by massively parallel sequencing. In this study, we focused on the comprehensive analysis of the NPHS2 gene. The histological classification of FSGS followed the Columbia classification.ResultsWe detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic NPHS2 variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of NPHS2-positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated NPHS2-associated FSGS patients was 50% (6/12), and Haplotype analysis predicted its origin to be a result of a founder effect. There is an identical V290M-related haplotype on all V290M alleles spanning a 0,7 Mb region flanking NPHS2 in Central European FSGS populations. The phenotype of the p.Val290Met NPHS2-associated FSGS demonstrated a later onset and a much milder course of the disease compared to other NPHS2 pathogenic variants associated with FSGS. The mean age of the FSGS diagnosis based on kidney biopsy evaluation was 31.2 ± 7.46 years. In 50% of all cases, the initial disease manifestation of proteinuria occurred only in adulthood, with 83% of these cases not presenting with edemas. One-third (33%) of the studied subjects progressed to ESRD (2 out of 6) at the mean age of 35.0 ± 2.82 years.ConclusionsWe identified the most prevalent pathogenic variant, p.Val290Met, in the NPHS2 gene among Czech adult FSGS patients, which has arisen due to a founder effect in Central Europe. The documented milder course of the disease associated with this variant leads to the underdiagnosis in childhood. We established the histopathological features of the NPHS2-associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment

Evaluation of Information Security System

Import 11/07/2012Cílem bakalářské práce je ohodnotit systém managementu bezpečnosti informací konkrétní firmy a upozornit na stávající problémy a zranitelná místa v informačním systému. První část bakalářské práce se věnuje pojmu bezpečnost informací, hrozbám informační bezpečnosti, dále detailně rozebírá charakteristiku normy ISO/IEC 27001:2005 a v závěru je popsán auditní proces. Ve druhé části je představena firma Finder a upřesněna metodika provedení analýzy. Ve třetí části je provedena analýza bezpečnosti informací v dané firmě. Každé konkrétní opatření normy je zhodnoceno dle míry reálného plnění.The goal of this thesis is to evaluate an information security management systém of the company Finder a.s company and highlight existing problems and vulnerabilities in the information system. The first part of the thesis is focused on terms like information security,information security threats and then analyzes in detail the characteristics of the norm ISO / IEC 27001:2005 and finally describes the audit process. In the second part is the company introduced and the methodology of the information security management analysis specified. In the third part is the information security management analysis of the company done. Each specific provision is evaluated according to the standard rateof fulfillment.115 - Katedra managementuvýborn

Audit of Security Information in a Selected Organization

Import 05/08/2014Diplomová práce se zabývá provedením auditu bezpečnosti informací ve společnosti ABC, s.r.o., vyhodnocení stavu všech oblastí bezpečnosti informací a následným navržením vhodných doporučení. Základem pro audit managementu bezpečnosti informací ve firmě ABC je norma ISO/IEC 27001:2005. Všeobecná možnost použití je vhodná pro zhodnocení bezpečnosti informací bez ohledu na rozsáhlost firmy, počet zaměstnanců či sféru podnikání. Kvůli stále sílící světové globalizaci je důležité, že norma ISO/IEC 27001:2005 je akceptována mezinárodně. První část diplomové práce se věnuje informační bezpečnosti, rozebírá jednotlivé typy přístupů kontroly bezpečnosti informací a v závěru teoretické části je popsán audit bezpečnosti informací. Následující část zahrnuje představení a popis firmy ABC, s.r.o. a specifikaci metodiky provedení auditu. V další fázi je proveden audit bezpečnosti informací ve firmě ABC, s.r.o. Jednotlivé části normy jsou analyzovány dle existence dokumentu a rozsahu skutečného provedení. Cílem diplomové práce je provést komplexní audit bezpečnosti informací firmy dle normy ISO/IEC 27001:2005 a v případě nedostačujícího plnění potřebných postupů navrhnout vhodné a prakticky přínosné opatření pro firmu ABC, s.r.o.This thesis deals with the audit of information security of the company ABC Ltd., with evaluation of the status of all areas of information security and designing appropriate recommendations . The basis for the audit of information security management in company ABC is standard ISO / IEC 27001:2005 . The standard is appropriate to evaluate the safety of information regardless of the size of the company, number of employees or business field . Due to increasing globalization it is important that the Standard ISO / IEC 27001:2005 is also internationally accepted . The first part of the thesis deals with information security, discusses the different types of control and information security. At the end of the theoretical part the audit of information security is discribed. The following section includes a description of the performance of ABC Ltd. and specification of the audit methodology . The next stage is to audit the security of information in company ABC Ltd. The individual parts of the standard are analyzed according to the existence of the document and the extent of actual implementation. The aim of the thesis is to conduct a comprehensive audit of information security companies according to ISO / IEC 27001:2005 and in case of insufficient fulfillment of the necessary procedures to design appropriate and practically useful measures for the company ABC Ltd.115 - Katedra managementudobř

Audit of Security Information in a Selected Organization

Import 05/08/2014Diplomová práce se zabývá provedením auditu bezpečnosti informací ve společnosti ABC, s.r.o., vyhodnocení stavu všech oblastí bezpečnosti informací a následným navržením vhodných doporučení. Základem pro audit managementu bezpečnosti informací ve firmě ABC je norma ISO/IEC 27001:2005. Všeobecná možnost použití je vhodná pro zhodnocení bezpečnosti informací bez ohledu na rozsáhlost firmy, počet zaměstnanců či sféru podnikání. Kvůli stále sílící světové globalizaci je důležité, že norma ISO/IEC 27001:2005 je akceptována mezinárodně. První část diplomové práce se věnuje informační bezpečnosti, rozebírá jednotlivé typy přístupů kontroly bezpečnosti informací a v závěru teoretické části je popsán audit bezpečnosti informací. Následující část zahrnuje představení a popis firmy ABC, s.r.o. a specifikaci metodiky provedení auditu. V další fázi je proveden audit bezpečnosti informací ve firmě ABC, s.r.o. Jednotlivé části normy jsou analyzovány dle existence dokumentu a rozsahu skutečného provedení. Cílem diplomové práce je provést komplexní audit bezpečnosti informací firmy dle normy ISO/IEC 27001:2005 a v případě nedostačujícího plnění potřebných postupů navrhnout vhodné a prakticky přínosné opatření pro firmu ABC, s.r.o.This thesis deals with the audit of information security of the company ABC Ltd., with evaluation of the status of all areas of information security and designing appropriate recommendations . The basis for the audit of information security management in company ABC is standard ISO / IEC 27001:2005 . The standard is appropriate to evaluate the safety of information regardless of the size of the company, number of employees or business field . Due to increasing globalization it is important that the Standard ISO / IEC 27001:2005 is also internationally accepted . The first part of the thesis deals with information security, discusses the different types of control and information security. At the end of the theoretical part the audit of information security is discribed. The following section includes a description of the performance of ABC Ltd. and specification of the audit methodology . The next stage is to audit the security of information in company ABC Ltd. The individual parts of the standard are analyzed according to the existence of the document and the extent of actual implementation. The aim of the thesis is to conduct a comprehensive audit of information security companies according to ISO / IEC 27001:2005 and in case of insufficient fulfillment of the necessary procedures to design appropriate and practically useful measures for the company ABC Ltd.115 - Katedra managementudobř

Lessons from two series by physicians and caregivers' self‐reported data in DDX3X ‐related disorders

International audienceAbstract Introduction and Methods We report two series of individuals with DDX3X variations, one (48 individuals) from physicians and one (44 individuals) from caregivers. Results These two series include several symptoms in common, with fairly similar distribution, which suggests that caregivers' data are close to physicians' data. For example, both series identified early childhood symptoms that were not previously described: feeding difficulties, mean walking age, and age at first words. Discussion Each of the two datasets provides complementary knowledge. We confirmed that symptoms are similar to those in the literature and provides more details on feeding difficulties. Caregivers considered that the symptom attention‐deficit/hyperactivity disorder were most worrisome. Both series also reported sleep disturbance. Recently, anxiety has been reported in individuals with DDX3X variants. We strongly suggest that attention‐deficit/hyperactivity disorder, anxiety, and sleep disorders need to be treated