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Opis: Autism spectrum disorders (ASD) represent a phenotypically heterogeneous group of patients that strongly intertwine with other neurodevelopmental disorders (NDDs), with genetics playing a significant role in their etiology. Whole exome sequencing (WES) has become predominant in molecular diagnostics for ASD by considerably increasing the diagnostic yield. However, the proportion of undiagnosed patients still remains high due to complex clinical presentation, reduced penetrance, and lack of segregation analysis or clinical information. Thus, reverse phenotyping, where we first identified a possible genetic cause and then determine its clinical relevance, has been shown to be a more efficient approach. WES was performed on 147 Slovenian pediatric patients with suspected ASD. Data analysis was focused on identifying ultrarare or “single event” variants in ASD-associated genes and further expanded to NDD-associated genes. Protein function and gene prioritization were performed on detected clinically relevant variants to determine their role in ASD etiology and phenotype. Reverse phenotyping revealed a pathogenic or likely pathogenic variant in ASD-associated genes in 20.4% of patients, with subsequent segregation analysis indicating that 14 were de novo variants and 1 was presumed compound heterozygous. The diagnostic yield was further increased by 2.7% by the analysis of ultrarare or “single event” variants in all NDD-associated genes. Protein function analysis established that genes in which variants of unknown significance (VUS) were detected were predominantly the cause of intellectual disability (ID), and in most cases, features of ASD as well. Using such an approach, variants in rarely described ASD-associated genes, such as SIN3B, NR4A2, and GRIA1, were detected. By expanding the analysis to include functionally similar NDD genes, variants in KCNK9, GNE, and other genes were identified. These would probably have been missed by classic genotype–phenotype analysis. Our study thus demonstrates that in patients with ASD, analysis of ultrarare or “single event” variants obtained using WES with the inclusion of functionally similar genes and reverse phenotyping obtained a higher diagnostic yield despite limited clinical data. The present study also demonstrates that most of the causative genes in our cohort were involved in the syndromic form of ASD and confirms their comorbidity with other developmental disorders.
Ključne besede: reverse phenotyping, single event variants, NDD-associated genes, GRIA1 gene, NR4A2 gene, SIN3B gene, autism, child
Objavljeno v DKUM: 12.12.2024; Ogledov: 0; Prenosov: 2
Celotno besedilo (6,36 MB)
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Opis: Stres je postal naš vsakdanji sopotnik, zato vse več ljudi išče načine za njegovo odpravo. V zadnjem času se povečuje število ljudi, ki se ukvarjajo s konjeništvom. Prav zaradi tega smo v diplomski nalogi raziskali sproščanje stresa s pomočjo konjev. V ta namen smo zbrali informacije o konjih, jahanju, stresu in sproščanju le-tega. Zanimala nas je evolucija konj, njihove karakteristike, konjeniški športi, komunikacija človek-konj, ter simptomi in sproščanje stresa. Raziskovalni del smo posvetili anketnemu vprašalniku, ki smo ga izvedli na skupini ljudi iz konjeniškega sveta (lastniki konj, ljubiteljski jahači in občudovalci konj). Ugotoviti smo hoteli v kolikšni meri so podvrženi stresu in koliko jim druženje s konji pripomore k boljšemu počutju. Rezultate anketnega vprašalnika smo ustrezno statistično obdelali. Ti so pokazali, da je ukvarjanje s konji zelo uspešno pri premagovanju stresa, predvsem če ga izvajajo redno.
Ključne besede: konji, jahanje, stres, sproščanje
Objavljeno v DKUM: 30.01.2012; Ogledov: 3044; Prenosov: 265
Celotno besedilo (369,77 KB)