Retinoblastoma and mental retardation microdeletion syndrome: clinical characterization and molecular dissection using array CGH.
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).
Caselli
R
R
Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
Speciale
C
C
Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
Pescucci
C
C
Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
Uliana
V
V
Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
Sampieri
K
K
Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
Bruttini
M
M
Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
Longo
I
I
Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
De Francesco
S
S
Department of Ophthalmology, Retinoblastoma Referral Center, Siena, Italy.
Pramparo
T
T
Biologia Generale e Genetica Medica, University of Pavia, Pavia, Italy.
Zuffardi
O
O
Biologia Generale e Genetica Medica, University of Pavia, Pavia, Italy.
Frezzotti
R
R
Department of Ophthalmology, University of Siena, Siena, Italy.
Acquaviva
A
A
Department of Pediatrics, University of Siena, Siena, Italy.
Hadjistilianou
T
T
Department of Ophthalmology, Retinoblastoma Referral Center, Siena, Italy.
Renieri
A
A
Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy. renieri@unisi.it.
Mari
F
F
Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
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