Unit:
Τομέας Υγείας - Μητέρας - ΠαιδιούLibrary of the School of Health Sciences
Dissertation committee:
Εμμανουήλ Καναβάκης, Σοφία Κίτσιου-Τζέλη, Μαρία Τζέτη
Original Title:
Ανίχνευση υπομικροσκοπικών χρωμοσωμικών διαταραχών σε ασθενείς με νοητική υστέρηση αγνώστου αιτιολογίας με τη μέθοδο των μικροσυστοιχιών γενωμικού συγκριτικού υβριδισμού (array-CGH)
Translated title:
Detection of submicroscopic chromosomal rearrangements in patients with intellectual disability of unknown etiology with the method of microarray comparative genomic hybridization (array-CGH)
Summary:
Intellectual Disability(ID) is characterized by clinical and genetic
heterogeneity, thus raising difficulties on genetic evaluation and diagnosis.
Hirtheto, only a few cases are detected by conventional techniques.The present
study focuses on the clinical application of array-CGH for first time in
Greece, as a first-tier diagnostic tool for the investigation of genetic basis
of unknown etiology ID in order to identify novel pathogenic copy number
variations(CNVs) and causal ID genes.Overall, 235 patients with variable
degrees of ID underwent array-CGH analysis.They had previously undergone a
series of other genetic tests (e.g conventional karyotype, RETT etc) which were
negative.High resolution 4x180K and 1x244K Agilent oligo-arrays(average
resolution ~13Kb) were used in this study.128 pathological CNVs microdeletion
and microduplication(0.015 to 18.4Mb) were detected in 89/235 patients (57
males, 32 females, mean age 6.25 years)(~38%), explaining partially or totally
the phenotype.52/128 CNVs were de novo, 10 were maternally inherited (one
mosaic), 3 were paternally inherited, whereas 2 were of both maternal and
paternal inheritance.Clinically relevant CNVs involve novel pathogenic
imbalances, some of them are recorded in DECIPHER and ISCA or/and are related
with known syndromes with atypical phenotype.Αrray-CGH is proven reliable and
valid providing more precise diagnosis, better genotype-phenotype correlations
as well as comprehensive genetic counselling.
Keywords:
Microarray Comparative Genomic Hybridization (array-CGH), Copy number variations (CNVs), Intellectual disability, Microdeletion/microduplication, Molecular karyotype
Number of index pages:
3-4
Number of references:
320
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