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A constitutional homozygous mutation in theRB1 gene in a patient with unilateral retinoblastoma
  1. *Departamento de Genética, Facultad de Ciencias Biológicas, Universidad de Valencia, C/ Doctor Moliner No 50, Burjassot, Valencia 46100, Spain
  2. †Unidad de Genética y Diagnóstico Prenatal, Hospital La Fe, Valencia, Spain
  1. Dr Nájera, Carmen.Najera{at}

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Editor—Retinoblastoma, a childhood tumour of the eye, is caused by inactivation in the developing human retina of both alleles of the tumour suppressor gene RB1. The product of the human RB1 gene (p110RB) is a nuclear phosphoprotein composed of 928 amino acids, which regulates the progression through the G1 phase of the cell cycle by interacting with transcription factors required for the expression of genes involved in cellular proliferation and differentiation.

In the non-hereditary form of the disease (∼60% of tumours), both mutations arise in retinal cells. Because in non-hereditary RB patients both RB1 mutations must occur in the same retinal cell, they are usually unilateral and unifocal. However, based on retrospective surveys of the offspring of patients with unilateral isolated retinoblastoma, Vogel1 estimated that in 10-12% of these patients the tumour is caused by germline cell mutations.

In the hereditary form of the disease (∼40% of RB patients), the initial mutation in one allele of the RB1gene is present in germline cells and leads to a predisposition to retinoblastoma. Since mutations in the second allele can occur independently in several retinal cells carrying this predisposing mutation, all patients with bilateral or unilateral multifocal RB are classified as having hereditary retinoblastoma. Most hereditary cases must result from “de novo” germline mutations, because only 10-15% of the hereditary cases have a previous family history of the disease. In familial cases, the predisposition to RB is transmitted as an autosomal dominant trait with 90% penetrance. Thus, in some familial cases, unaffected or only unilaterally affected subjects can be identified who can transmit the mutant gene.1 The “two hit” hypothesis predicts the existence of these cases that form part of a Poisson distribution in which, by chance, the second random mutation does not occur.2 …

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