title: Cerebroretinal microangiopathy with calcifications and cysts associated with CTC1 and NDP mutations.
abstract: Mutations in the conserved telomere maintenance component 1 (CTC1) gene were recently described in Coats plus syndrome and in cerebroretinal microangiopathy with calcifications and cysts. Norrie disease protein (NDP) gene was found mutated in Norrie disease, in Familial Exudative Vitreoretinopathy, and in Coats syndrome. Here we describe a boy affected by Norrie disease who developed typical features of cerebroretinal microangiopathy with calcifications and cysts. Direct sequencing of the CTC1 and NDP genes in this patient shows the presence of compound heterozygosity for 2 mutations in CTC1 (c.775G>A, pV259M and a novel microdeletion c.1213delG) and a missense mutation in the NDP gene (c.182T>C, p.L61P). Based on these genetic findings and on the expression of both genes in endothelial cells, we postulate that microangiopathy might be a primary underlying pathologic abnormality in cerebroretinal microangiopathy with calcifications and cysts. This hypothesis is further supported by magnetic resonance imaging (MRI) data showing multiple minute calcifications in the deep gray nuclei and in terminal arteriolar zones.
authors.affiliation: 1Department of Child Neuropsychiatry and Neurorehabilitation, "Eugenio Medea" Scientific Institute, Bosisio Parini, Lecco, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Romaniello
authors.forename: Filippo
authors.initials: F
authors.lastname: Arrigoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Citterio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tonelli
authors.forename: Cinzia
authors.initials: C
authors.lastname: Sforzini
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rizzari
authors.forename: Marco
authors.initials: M
authors.lastname: Pessina
authors.forename: Fabio
authors.initials: F
authors.lastname: Triulzi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bassi
authors.forename: Renato
authors.initials: R
authors.lastname: Borgatti
mesh_terms: D001259:Ataxia / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics*; D002114:Calcinosis / Q000235:genetics*; D020863:Central Nervous System Cysts / Q000235:genetics*; D002648:Child; D005136:Eye Proteins / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics*; D008297:Male; D009128:Muscle Spasticity / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012164:Retinal Diseases / Q000235:genetics*; D012640:Seizures / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics*
chemical_list: C544945:Ctc1 protein, human; D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins; D034501:Telomere-Binding Proteins