A unique case of Bloom syndrome with a combination of genetic hits: A lesson from trio‑based exome sequencing: A case report

Wayhelova, Marketa; Vallová, Vladimíra; Brož, Petr; Mikulášová, Aneta; Machackova, Dominika; Filková, Hana; Smetana, Jan; Takacsova, Alena; Gaillyová, Renata; Kuglík, Petr

doi:10.3892/mmr.2023.12997

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…After excluding common LCSHs and manual curation the CMA outputs and SNV/indel analysis using trio ES data, no additional LCSHs harbouring homozygous causative variants were identified. A mosaic LCSH affecting the short arm of chromosome 11 (11p) was uncovered in the index case 44-P as described in our previous study [ 16 ].…”

Section: Resultsmentioning

confidence: 79%

Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders

Wayhelova,

Vallova,

Broz

et al. 2024

Orphanet J Rare Dis

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Background Neurodevelopmental disorders (NDDs) and/or associated multiple congenital abnormalities (MCAs) represent a genetically heterogeneous group of conditions with an adverse prognosis for the quality of intellectual and social abilities and common daily functioning. The rapid development of exome sequencing (ES) techniques, together with trio-based analysis, nowadays leads to up to 50% diagnostic yield. Therefore, it is considered as the state-of-the-art approach in these diagnoses. Results In our study, we present the results of ES in a cohort of 85 families with 90 children with severe NDDs and MCAs. The interconnection of the in-house bioinformatic pipeline and a unique algorithm for variant prioritization resulted in a diagnostic yield of up to 48.9% (44/90), including rare and novel causative variants (41/90) and intragenic copy-number variations (CNVs) (3/90). Of the total number of 47 causative variants, 53.2% (25/47) were novel, highlighting the clinical benefit of ES for unexplained NDDs. Moreover, trio-based ES was verified as a reliable tool for the detection of rare CNVs, ranging from intragenic exon deletions (GRIN2A, ZC4H2 genes) to a 6-Mb duplication. The functional analysis using PANTHER Gene Ontology confirmed the involvement of genes with causative variants in a wide spectrum of developmental processes and molecular pathways, which form essential structural and functional components of the central nervous system. Conclusion Taken together, we present one of the first ES studies of this scale from the central European region. Based on the high diagnostic yield for paediatric NDDs in this study, 48.9%, we confirm trio-based ES as an effective and reliable first-tier diagnostic test in the genetic evaluation of children with NDDs.

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Section: Resultsmentioning

confidence: 79%

Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders

Wayhelova,

Vallova,

Broz

et al. 2024

Orphanet J Rare Dis

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“…O gene BLM (15q26.1) ou também denominado RECQL3, é responsável por codificar uma proteína nuclear intracelular pertencente à família RecQ de helicases de DNA 3' a 5', logo, crucial nos processos complexos de regulação do ciclo celular e reparo do DNA para manter a estabilidade do genoma (Wayhelova et al, 2023).…”

Section: Discussionunclassified

Síndrome de Bloom: uma abordagem diagnóstica, evolução clínica e revisão

Nascimento,

Tavares,

Rodovalho

et al. 2023

Braz. J. Hea. Rev.

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Introdução: A Síndrome de Bloom, também conhecida como síndrome de Bloom-Torre-Machacek, é uma doença genética rara e hereditária, classificada como distúrbio de instabilidade cromossômica. Caracterizada por danos frequentes aos cromossomos, essa síndrome apresenta uma ampla variedade de manifestações clínicas que podem afetar múltiplos sistemas do corpo. Apresentação do Caso: Um garoto de 9 anos, residente do estado de Goiás, foi levado por seus pais atenciosos a uma consulta pediátrica devido a preocupações com seu crescimento subótimo, frequentes erupções cutâneas e notável sensibilidade à luz. Carlos nasceu de uma gravidez sem complicações, e seu desenvolvimento inicial foi típico. Ele é o filho mais novo de dois irmãos, e não há um histórico familiar conhecido de doenças genéticas. Discussão: Nesta síndrome (de Bloom), é imprescindível serem abordados aspectos essenciais da doença, incluindo sua epidemiologia, etiologia genética e herança autossômica recessiva. Serão analisados critérios diagnósticos atualmente aceitos, considerando os achados clínicos mais comuns, como crescimento comprometido, fotossensibilidade, predisposição a infecções, anormalidades dermatológicas, risco aumentado de câncer e problemas respiratórios. Uma abordagem multidisciplinar para o diagnóstico precoce e o tratamento adequado será discutida, destacando a importância de testes genéticos, aconselhamento genético e acompanhamento médico regular para pacientes com Síndrome de Bloom. Além disso, serão abordadas as opções de tratamento disponíveis, focadas no manejo dos sintomas e na prevenção de complicações, bem como a importância do apoio psicológico e terapêutico para melhorar a qualidade de vida dos pacientes. Conclusão: Portanto, é fundamental promover o entendimento da doença, facilitando a identificação e a intervenção precoce, para melhorar o prognóstico e o bem-estar dos indivíduos afetados por essa rara e complexa síndrome genética.

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Flow cytometry for extracellular vesicle characterization in COVID-19 and post-acute sequelae of SARS-CoV-2 infection

Fanelli,

Petrone,

Chirico

et al. 2024

Extracell Vesicles Circ Nucleic Acids

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Infection with SARS-CoV-2, the virus responsible for COVID-19 diseases, can impact different tissues and induce significant cellular alterations. The production of extracellular vesicles (EVs), which are physiologically involved in cell communication, is also altered during COVID-19, along with the dysfunction of cytoplasmic organelles. Since circulating EVs reflect the state of their cells of origin, they represent valuable tools for monitoring pathological conditions. Despite challenges in detecting EVs due to their size and specific cellular compartment origin using different methodologies, flow cytometry has proven to be an effective method for assessing the role of EVs in COVID-19. This review summarizes the involvement of plasmatic EVs in COVID-19 patients and individuals with Long COVID (LC) affected by post-acute sequelae of SARS-CoV-2 infection (PASC), highlighting their dual role in exerting both pro- and antiviral effects. We also emphasize how flow cytometry, with its multiparametric approach, can be employed to characterize circulating EVs, particularly in infectious diseases such as COVID-19, and suggest their potential role in chronic impairments during post-infection.

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A unique case of Bloom syndrome with a combination of genetic hits: A lesson from trio‑based exome sequencing: A case report

Cited by 3 publications

References 42 publications

Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders

Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders

Síndrome de Bloom: uma abordagem diagnóstica, evolução clínica e revisão

Flow cytometry for extracellular vesicle characterization in COVID-19 and post-acute sequelae of SARS-CoV-2 infection

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