Molecular genetic screening in patients with craniosynostosis

Doctoral Dissertation uoadl:2874936 63 Read counter

Τομέας Υγείας - Μητέρας - Παιδιού
Library of the School of Health Sciences
Deposit date:
Goumenos Athanasios
Dissertation committee:
Συνοδινού Ιωάννα Ραχήλ, Καθηγήτρια, Ιατρική, ΕΚΠΑ
Φρυσίρα-Κανιούρα Ελένη, Καθηγήτρια, Ιατρική, ΕΚΠΑ
Περβανίδου Παναγιώτα, Επίκουρη Καθηγήτρια, Ιατρική, ΕΚΠΑ
Τζέτη Μαρία, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
Σιαχανίδου Σουλτάνα, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
Πιπέρη Χριστίνα, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
Πονς-Ροντρίγκεθ, Μαρία Ρόζε, Επίκουρη Καθηγήτρια, Ιατρική, ΕΚΠΑ
Original Title:
Μοριακή γενετική διερεύνηση ασθενών με σύνδρομα κρανιοσυνοστέωσης
Translated title:
Molecular genetic screening in patients with craniosynostosis
Craniosynostosis is a condition where one or more of the cranial sutures fuse prematurely. The prevalence is estimated to be in the region of 1 out of 1,500 births. Craniosynostosis may occur under three distinct phaenomena: 1) Abnormal brain growth, 2) Chemical agents/ mutagens and 3) Genetic aetiology. It can be classified as syndromic or non-syndromic whether additional features are present or not, respectively.
The genetic background of craniosynostosis is moderately understood. Almost 60% of the patients tend to be under-diagnosed, whereas 40% have large-scale chromosomic anomalies or intragenic mutations/SNPs in a variety of genes. The later usually exhibit a more severe phenotype than those of the first category. Additionally it has been observed that of the four sutures the most commonly affected is the Sagittal, followed by the Coronal, then the Metopic and finally the Lamboid.
The objective of this thesis was to identify and study previously known or newly discovered mutations in genes related to craniosynostosis. A further aim was to expand the knowledge of the underlying mechanisms governed by those genes. Additionally genetic diagnosis, in previously undiagnosed patients, was achieved. For this thesis to be completed a total of 67 samples were collected and a series of molecular testing was performed in all of them.
Concluding, we managed to identify novel or previously characterised mutations in the following genes: FGFR1, FGFR2, FGFR3, TCF12, FREM1 and NAA10. Two of them, found in FGFR2 and TCF12 were of particular interest, as they helped us to better understand the mechanisms in which those genes act through cranial suture moprhogenesis. All findings were given to the patients or their parents further helping them with genetic counselling.
Main subject category:
Health Sciences
Craniosynostosis, Genetics, Syndromes, Dysplasias, Next generation sequencing
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