Porphyria cutanea tarda (PCT) is the most common chronic porphyria, with approximate prevalence of 1:10,000. PCT is frequently associated with hepatitis C virus (HCV), malignant lymphoma and iron overload. Here, we present a case of PCT onset subsequent to hepatitis E virus infection (HEV), characterised by symptoms including skin fragility, haemorrhagic bullous skin exanthema, and onycholysis. The patient was successfully treated by erythrocytapheresis and hydroxychloroquine. After exclusion of other possible causes of PCT, HEV infection was identified as the likely trigger of the disease in this genetically predisposed individual, representing the first reported instance of such an association. Erythrocytapheresis emerged as a viable alternative to phlebotomy for PCT treatment. This case underscores the significance of considering HEV infection in the aetiology of PCT and highlights erythrocytapheresis as a promising therapeutic approach (Ref. 8).

• Publikační typ
• abstrakt z konference MeSH

LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:282-285.

• MeSH
• časové faktory MeSH
• chelátory škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• hepatolentikulární degenerace diagnostické zobrazování   farmakoterapie   metabolismus   MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• měď analýza   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• penicilamin škodlivé účinky   terapeutické užití   MeSH
• počítačové zpracování obrazu MeSH
• šedá hmota diagnostické zobrazování   účinky léků   MeSH
• studie případů a kontrol MeSH
• tkáňová distribuce MeSH
• ultrasonografie dopplerovská transkraniální MeSH
• železo analýza   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Mutace v MECP2 genu jsou nejčastěji spojovány s Rettovým syndromem, závažnou pervasivní vývojovou poruchou a jedním z mála neurovývojových onemocnění, u kterých je dnes jednoznačně známa genetická příčina. Jelikož se fenotypové projevy Rettova syndromu do značné míry překrývají s projevy např. dětského autismu a Angelmanova syndromu, pravděpodobně se v jejich patogenezi uplatňují stejné procesy. Nedávná identifikace MECP2 mutací u pacientů s těmito a dalšími typy mentální retardace tuto teorii potvrdila a umožnila tak rozšířit základní i aplikovaný výzkum MECP2 genu a jeho produktu na širší spektrum onemocnění. V předkládaném projektu bude studováno zastoupení MECP2 mutací v jednotlivých typech MECP2 onemocnění a dále bude pomocí korelace genotypu funkčních polymorfismů v kandidátních modulačních genech se závažností fenotypu sledován vliv dalších genetických faktorů na základní fenotyp.; Mutations in the MECP2 gene are mostly identified in patients with Rett syndrome, a severe pervasive developmental disorder and one of a few neurodevelopmental disorders with a known genetic cause. The clinical features of Rett syndrome overlap with autism and Angelman syndrome and therefore it has been suggested that they may share common pathological pathways. Recent identification of MECP2 mutations in patients with autism, Angelman syndrome and other types of mental retardation supports this theory. It also allows to extend the basic and applied research of the MECP2 gene and its product to wider spectrum of disorders. In this project we will study the frequency and type of MECP2 mutations in MECP2 disorders and correlate the severity of clinical phenotype with genotypes of functional polymorphisms in several candidate modifier genes.

• MeSH
• autistická porucha diagnóza   genetika   MeSH
• diagnostické techniky molekulární MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• mentální retardace vázaná na chromozom X MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• polymorfismus genetický MeSH
• prenatální diagnóza MeSH
• protein 2 vázající methyl-CpG MeSH
• regulace genové exprese MeSH
• Rettův syndrom diagnóza   genetika   MeSH
• Geografické názvy
• Česká republika MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• genetika, lékařská genetika
• biologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

INTRODUCTION: Wilson's disease (WD) is a hereditary disorder caused by ATP7B mutations resulting in systemic copper accumulation. WD may manifest as early-adulthood parkinsonism; and atypical cases may be difficult to distinguish from early-onset Parkinson's disease (EO-PD), a neurodegenerative disorder with onset ≤40 years of age. The aim of our study was to compare transcranial sonography (TCS)-magnetic resonance fusion imaging in WD and EO-PD and examine whether TCS can provide clinically useful information. METHODS: We examined 22 WD, 16 EO-PD, and 24 healthy control subjects. We measured echogenicity and determined presence of MRI signal changes in T2-weighted images in the substantia nigra (SN) and lentiform nucleus (NL). TCS with the capability of magnetic resonance fusion and Virtual Navigator was used. The echogenicity indices of SN and NL were processed using digital image analysis to eliminate subjective evaluation errors. RESULTS: Mean SN echogenicity index in EO-PD (39.8 ± 5.9 [SD]) was higher compared to WD (28.0 ± 4.6, p < 0.0001) and control subjects (28.8 ± 4.9, p < 0.0001). Mean NL echogenicity index was higher in WD (117.5 ± 37.0) compared to EO-PD (61.6 ± 5.4, p < 0.0001) and control subjects (54.9 ± 11.2, p < 0.0001). The SN hyperechogenicity had sensitivity 93.8%, and specificity 90.9%, while the NL hyperechogenicity had sensitivity 95.5% and specificity 93.8% for differentiation of WD and EO-PD. NL hyperechogenicity was more pronounced in WD subjects with putaminal MRI T2 hyperintensity (p < 0.05) but was also present in subjects without MRI abnormality. CONCLUSIONS: There are distinct TCS findings in WD and EO-PD complementary to MRI that can be utilized as highly sensitive and specific biomarkers of these disorders.

• MeSH
• biologické markery MeSH
• corpus striatum diagnostické zobrazování   MeSH
• dospělí MeSH
• hepatolentikulární degenerace diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie normy   MeSH
• multimodální zobrazování MeSH
• Parkinsonova nemoc diagnostické zobrazování   MeSH
• senzitivita a specificita MeSH
• ultrasonografie dopplerovská transkraniální normy   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases.

• MeSH
• epilepsie genetika   MeSH
• fenotyp MeSH
• genetická predispozice k nemoci * MeSH
• lidé MeSH
• mutace * MeSH
• nemoci mozku genetika   MeSH
• protein-serin-threoninkinasy genetika   MeSH
• Rettův syndrom genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder characterized by developmental regression with loss of motor, communication and social skills, onset of stereotypic hand movements and often seizures. RTT is primarily caused by de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). We established a high-resolution melting (HRM) technique for mutation scanning of the MECP2 gene and performed analyses in Czech patients with RTT, autism spectrum conditions and intellectual disability with Rett-like features. In the cases with confirmed MECP2 mutations, we determined X-chromosome inactivation (XCI), examined the relationships between genotype and clinical severity and evaluated the modifying influence of XCI. Our results demonstrate that HRM analysis is a reliable method for the detection of point mutations, small deletions and duplications in the MECP2 gene. We identified 29 pathogenic mutations in 75 girls, including four novel mutations: c.155_1189del1035;909_932inv;insC, c.573delC, c.857_858dupAA and c.1163_1200del38. Skewed XCI (ratio >75%) was found in 19.3% of the girls, but no gross divergence in clinical severity was observed. Our findings confirm a high mutation frequency in classic RTT (92%) and a correlation between the MECP2 mutation type and clinical severity. We also demonstrate limitations of XCI in explaining all of the phenotypic differences in RTT.

• MeSH
• alely MeSH
• dítě MeSH
• exony MeSH
• fenotyp * MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie * MeSH
• genotyp * MeSH
• inaktivace chromozomu X MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• mladiství MeSH
• mutace * MeSH
• mutační analýza DNA MeSH
• předškolní dítě MeSH
• protein 2 vázající methyl-CpG genetika   MeSH
• Rettův syndrom diagnóza   genetika   MeSH
• techniky amplifikace nukleových kyselin MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakty MeSH

OBJECTIVE: The aim of the study is to determine the frequency of parkin allelic variants in Czech early-onset Parkinson's disease patients and healthy controls. METHODS: A total of 70 early-onset Parkinson's disease patients (age at onset ≤40 years) and 75 controls were screened for the sequence variants and exon rearrangements in the parkin gene. RESULTS: Parkin mutations were identified in five patients (7.1%): the p.R334C point mutation was present in one patient, four patients had exon deletions. The detected mutations were observed in the heterozygous state except one homozygous deletion of the exon 4. No mutations were obtained in control subjects. A novel sequence variant p.V380I (c.1138G>A) was identified in one control. Non-pathogenic polymorphisms p.S167N and p.D394N were seen in similar percentage in patients and controls, polymorphism p.V380L was almost twice as frequent in controls as in patients. CONCLUSIONS: Our study contributes to the growing body of evidence on the low frequency of the parkin mutations in the early-onset Parkinson's disease suggesting the potential role of other genes in the pathogenesis of the disease.

• MeSH
• genotyp MeSH
• lidé MeSH
• mutace * MeSH
• Parkinsonova nemoc genetika   MeSH
• sekvenční delece MeSH
• ubikvitinligasy genetika   MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH