title: Retinoblastoma and mental retardation microdeletion syndrome: clinical characterization and molecular dissection using array CGH.
abstract: We describe three patients with retinoblastoma, dysmorphic features and developmental delay. Patients 1 and 2 have high and broad forehead, deeply grooved philtrum, thick anteverted lobes and thick helix. Patient 1 also has dolicocephaly, sacral pit/dimple and toe crowding; patient 2 shows intrauterine growth retardation and short fifth toe. Both patients have partial agenesis of corpus callosum. Patient 3 has growth retardation, microcephaly, thick lower lip and micrognathia. Using array-comparative genomic hybridization (CGH), we identified a 13q14 de novo deletion in patients 1 and 2, while patient 3 had a 7q11.21 maternally inherited deletion, probably not related to the disease. Our results confirm that a distinct facial phenotype is related to a 13q14 deletion. Patients with retinoblastoma and malformations without a peculiar facial phenotype may have a different deletion syndrome or a casual association of mental retardation and retinoblastoma. Using array-CGH, we defined a critical region for mental retardation and dysmorphic features. We compared this deletion with a smaller one in a patient with retinoblastoma (case 4) and identified two distinct critical regions, containing 30 genes. Four genes appear to be good functional candidates for the neurological phenotype: NUFIP1 (nuclear fragile X mental retardation protein 1), HTR2A (serotonin receptor 2A), PCDH8 (prothocaderin 8) and PCDH17 (prothocaderin 17).
authors.affiliation: Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Caselli
authors.affiliation: Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Speciale
authors.affiliation: Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pescucci
authors.affiliation: Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Uliana
authors.affiliation: Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
authors.forename: K
authors.initials: K
authors.lastname: Sampieri
authors.affiliation: Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bruttini
authors.affiliation: Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Longo
authors.affiliation: Department of Ophthalmology, Retinoblastoma Referral Center, Siena, Italy.
authors.forename: S
authors.initials: S
authors.lastname: De Francesco
authors.affiliation: Biologia Generale e Genetica Medica, University of Pavia, Pavia, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Pramparo
authors.affiliation: Biologia Generale e Genetica Medica, University of Pavia, Pavia, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Zuffardi
authors.affiliation: Department of Ophthalmology, University of Siena, Siena, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Frezzotti
authors.affiliation: Department of Pediatrics, University of Siena, Siena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Acquaviva
authors.affiliation: Department of Ophthalmology, Retinoblastoma Referral Center, Siena, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Hadjistilianou
authors.affiliation: Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy. renieri@unisi.it.
authors.forename: A
authors.initials: A
authors.lastname: Renieri
authors.affiliation: Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mari
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics; D016133:Polymerase Chain Reaction; D019572:Retinal Neoplasms / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics*; D013577:Syndrome