Study of the relationship genotype/phenotype in retinoblastoma
type: Dataset
description: Retinoblastoma is the most common intraocular childhood cancer and occurs when both alleles of the RB1 gene are inactivated in the retina. In patients without genetic predisposition, the two mutations occurred in a single unique retinal cell. In subjects with a genetic predisposition to retinoblastoma, the first RB1 mutation is found in the germline and the second appears as a somatic mutation. Germline carriers usually develop bilateral or multifocal tumors and the diagnosis is earlier. However, some rare families exhibit low penetrance and variable expressivity of the disease because bilaterally affected, unilaterally affected, and unaffected mutation carriers are known to coexist. The existence of genetic modifiers in retinoblastoma therefore appears highly probable and must be considered. The lack of penetrance and the variable expressivity could be the sum of three independent causes. The presence of a mosaic can affect the phenotype, the nature of the mutation can drive low penetrance and particular phenotype like psychomotor delay in case of large genomic deletions and genetic modifier factors could modulate the phenotype. These three major keys have been studied in order to highlight the relations between the phenotype and the genotype. Firstly, the consequences of mosaicism have been illustrated by a prenatal diagnosis concerning a couple with a bilateral retinoblastoma-affected male patient who requested five successive prenatal diagnoses and in whom RB1 mutation mosaicism had important implications. Implications of mosaicism in genetic counseling have been discussed and taken into consideration in order to limit bias in the two following genotype/phenotype studies. Secondly, the association between whole germline monoallelic deletions of the RB1 gene and psychomotor delay was studied by a high-resolution CGH array focusing on RB1 and its flanking region. Comparative analysis detected a four megabase critical interval including a candidate gene, protocadhe…
landing page: https://theses.hal.science/tel-00794201
identifier: NNT: 2012PA05T059
keyword: cgh
keyword: facteurs-modificateurs
keyword: faible-penetrance
keyword: infoeu-reposemanticsdoctoralthesis
keyword: low-penetrance
keyword: mdm2
keyword: modifier-gene
keyword: mosaicism
keyword: mosaique
keyword: psychomotor-delay
keyword: retard-psychomoteur
keyword: retinoblastoma
keyword: retinoblastome
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: theses
issued: 2026-05-14T04:29:39.425000
modified: 2026-05-14T04:29:39.425007
language: fr
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

Study of the relationship genotype/phenotype in retinoblastoma
type: Distribution
format: HTML
access URL: https://theses.hal.science/tel-00794201
issued: 2026-05-14T04:29:39.432454
modified: 2026-05-14T04:29:39.378399