Τομέας Υγείας - Μητέρας - ΠαιδιούLibrary of the School of Health Sciences
Σοφία Κίτσιου-‐Τζέλη, Καθηγήτρια, Ιατρική, ΕΚΠΑ
Εμμανουήλ Καναβάκης, Ομότιμος Καθηγητής, Ιατρική, ΕΚΠΑ
Μαρία Τζέτη, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
Ελένη Φρυσίρα, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
Παναγιώτα Περβανίδου, Επίκουρη Καθηγήτρια, Ιατρική, ΕΚΠΑ
Μαρία Ροζέ Πονς-‐Ροντρίγκεθ, Επίκουρη Καθηγήτρια, Ιατρική, ΕΚΠΑ
Γιώργος Βάρτζελης, Λέκτορας, Ιατρική, ΕΚΠΑ
Ανίχνευση υπομικροσκοπικών χρωμοσωμικών διαταραχών σε ασθενείς με αυτιστικές διαταραχές με την μέθοδο των μικροσυστοιχιών συγκριτικού γενωμικού υβριδισμού arrayCGH
Autistic Spectrum Disorders (ASD) or autism is a group of heterogeneous lifelong neurodevelopmental disorders that usually develop during childhood and are characterized by impaired communication skills and social interaction and repetitive behavior. The age of onset is usually before the age of three years old and the diagnosis is based on behavioral criteria and detailed clinical examination. The most recent studies (2012) estimate the prevalence of ASDs at 1/68 children in the age of 8 years old (1,5%) in the USA. The ASDs are considered a multifactorial disorder and many factors such as genetic, epigenetic, metabolical, hormonal, immunological, neuroanatomical, neurophysiological, gastrointestinal and other systematic comorbidities are implicated in the pathogenetic mechanisms. The genetic contribution of autism is of great significance and thus, in the present dissertation, the different models of inheritance that help explain the increased frequency of ASDs in some families are described in detail, together with the major neurobiological mechanisms that lead to the phenotype. Chromosomal Microarray Analysis (CMA) is currently considered a first tier diagnostic assay for the investigation of Autism Spectrum Disorders (ASD), Developmental Delay (DD) and Intellectual Disability (ID) of unknown etiology. High resolution arrays were utilized for the identification of Copy Number Variations (CNVs) in 195 ASD patients of Greek origin (126 males, 69 females). CMA resulted in the detection of 65 CNVs, excluding the known polymorphic CNPs also found in the database of genomic variants (DGV), for 51/195 patients (26.1%). Parental DNA testing in 20/51 patients revealed that 15 CNVs were de novo, 3 of paternal and 2 of maternal origin. The majority of the 65 CNVs were deletions (66.1%), of which 5 on the X‐chromosome while the duplications, of which 7 on the X‐chromosome, were rarer (22/65, 33.8%). Fifty-one CNVs from a total of 65, reported for our cohort of ASD patients, were of diagnostic significance and well described in the literature while 14 CNVs (8 losses, 6 gains) were characterized as Variants of Unknown Significance (VOUS) and need further investigation. Amongst the 51 patients 39 carried one CNV, 10 carried two CNVs and 2 carried three CNVs. The use of CMA, its clinical validity and utility was assessed.
Autism Spectrum Disorders, Intellectual Disability, array Comparative Genomic Hybridization, arrayCGH, CNVs
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