Dissertation committee:
Βασιλική Παπαευαγγέλου, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Αναστάσιος Παπαδημητρίου, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αργύριος Ντινόπουλος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Πρίφτης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μελπωμένη Πέππα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Βασίλειος Κοντογεωργάκος, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αχιλλέας Αττιλάκος, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
The osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal
recessive disorder, characterized by impaired bone accrual and congenital or
early-onset blindness. Loss of function mutations in the gene encoding lowdensity
lipoprotein receptor-related protein 5 (LRP5), either in homozygous or
compound heterozygous state, has been established as the genetic defect of
the disease. We report the clinical, biochemical and genetic evaluation of ten
new cases of OPPG in eight related nuclear families in Greece. Mutational
screening of the patients’ LRP5 gene revealed the c.2409_2503+79del
deletion in homozygous state, expected to result in a truncated protein.
Among the 44 individuals of the pedigree tested, 26 were identified to harbor
one mutant allele. All patients had congenital ocular impairment. Seven
patients who underwent DXA evaluation presented with osteopenia and four
of them received bisphosphonates. Treatment resulted in BMD improvement,
decrease of bone pain and maintenance of normal PTH and calcium
homeostasis, without however fully counteracting osteoporosis. This is the
first report of the homozygous c.2409_2503+79del (G804_G835delfsX49)
deletion in the LRP5 gene in patients with OPPG in the Mediterranean rim,
presenting in detail the
