Unit:
Τομέας ΚλινικοεργαστηριακόςLibrary of the School of Health Sciences
Dissertation committee:
1. Καναβάκης Εμμανουήλ, Καθηγητής, Ιατρική, ΕΚΠΑ
2. Κίτσιου-Τζέλη Σοφία, Καθηγήτρια, Ιατρική, ΕΚΠΑ
3. Τσολιά Μαρία, Καθηγήτρια, Ιατρική, ΕΚΠΑ
4. Χαρμανδάρη Ευαγγελία, Καθηγήτρια, Ιατρική, ΕΚΠΑ
5. Τζέτη Μαρία, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
6. Φρυσίρα-Κανιούρα Ελένη, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
7. Καττάμης Αντώνης, Καθηγητής, Ιατρική, ΕΚΠΑ
Original Title:
Έλεγχος ασθενών με συγγενείς ανωμαλίες με τη μέθοδο του μοριακού καρυοτύπου/ Array-CGH: συσχέτιση του γονότυπου με τον φαινότυπο
Translated title:
Control of patients with congenital abnormalities using the molecular karyotype / Array-CGH: correlation of the genotype with the phenotype
Summary:
The definition of congenital anomalies refers to any structural, functional, metabolic disorder that occurs in the fetus during prenatal development and becomes evident either at birth or later in neonatal / infant or subsequent age, resulting in physical or mental disability. It is estimated that at least 2% of fetuses and infants have major congenital abnormalities, reaching about 6-7% in systematic registers of congenital abnormalities. They account for 1/3 of pediatric input, and about 20 to 25% of the causes of death during the perinatal period, occupying the first cause of death in infancy throughout the Western world. In 30% of infants with structural anomalies that will survive the perinatal period, their life in neonatal and early infancy is still threatened. They are the second leading cause of death among ages between 1 and 5 years following childhood accidents while they are among at the top five causes of death during adolescence.
Congenital abnormalities with or without mental retardation/ autism spectrum disorders (ASD) may be due to chromosomal abnormalities identified in about 1/200 neonates by conventional karyotype. However, classical cytogenetic analysis is not able to reliably detect genomic rearrangements of less than 5 to 10 megabases (Mb), or the chromosomal origin of the marker chromosome, nor the exact breakage position of the rearrangements. Thus, with the established karyotype genetic testing for congenital abnormalities, chromosomal abnormalities are only revealed at 0.5%, while more than 25% of patients with deformities and mental retardation remain undiagnosed.
The Molecular Kayrotype technology with array-CGH microarrays further improves diagnostic genetic tests and bridges the gap between cytogenetic (conventional karyotype) and molecular genetic analysis . With the application of the Molecular Karyotype, submicroscopic unbalanced chromosomal rearrangements of several kilobases (Kb) to several megabases (Mb) are detected throughout the chromosome, contributing to a reduction in the incidence of undiagnosed cases of multiple congenital abnormalities, mental retardation or/and peculiar faces.
In the context of this PhD for the detection of Copy Number Variations (CNVs), high resolution microarrays were used in 197 patients with relapsing abnormalities, with or without mental retardation / ASD (92 males, 105 females), aged from 1 day to 35 years old.
Array-CGH identified only Copy Number Polymorphisms (CNPs) in 75 patients, pathological CNVs not associated with congenital abnormalities in 41 patients and pathological CNVs associated with congenital abnormalities in 81 patients (41%).20 out of 81 patients had congenital abnormalities, 57 out of 81 patients had congenital abnormalities with mental retardation and 4 out of 81 patients had congenital abnormalities with mental retardation and ASD.
The majority of the 133 CNVs found in 81 patients were microdeletions (89/133) with a frequency of 67%, while the microduplications were less frequent. In 47 patients with congenital abnormalities the pathological phenotype was associated with 1 CNV, in 21 cases with 2 CNVs, while in 13 patients with 3 or more CNVs. The size of detected CNVs varies from 8 Kb to 22.5 Mb. In a total of 62/81 patients have been identified with known microduplications and microdeletions syndromes that have been described in the literature in individuals with the same or similar clinical phenotype.
Main subject category:
Health Sciences
Keywords:
Molecular karyotype
array-CGH
Congenital anomalies
Number of references:
135
