A 20.5-Mb germline deletion of 13q13.1-->q14.3 and somatic mutations of the RB1 gene in an 8-year-old girl with unilateral retinoblastoma, developmental delay and mental retardation.

The 8-year-old female patient was the first child of a healthy and unrelated couple. Both the mother and father were 28 years old at her birth. There was no family history of congenital malformations. She was born uneventfully at 38 weeks of gestation with a birth weight of 2,430 g ( We report on clinical and molecular findings in an 8-year-old girl with unilateral retinoblastoma, developmental delay, mental retardation, a germline RBl deletion and somatic mutations of the RBl gene. The present case demonstrates concomitant germline large cytogenetic 13q deletion and somatic mutations in the RBl gene in unilateral retinoblastoma. The frequency of cytogenetic 13q deletion in retinoblastoma patients has been reported as 3.3-11.3% (4). In a study of frequency of 13q abnormalities among patients with retinoblastoma, Bunin et al. (2) found 13ql4 deletion in about 4.9% (6/123) of patients with unilateral retinoblastoma. In retinoblastoma patients with cytogenetic 13q deletion, an excess of patients with unilateral retinoblastoma has been observed (1-3). It has been postulated that among patients with a germline cytogenetic 13q deletion, fewer tumors may arise in those patients, giving more patients with a unilateral tumor (1,2). Albrecht et al.\) suggested that carriers of cytogenetic and submicroscopic whole RBl gene deletions often have unilateral retinoblastoma only. Bunin et al. (2) hypothesized that if the first hit is loss of a significant portion of chromosome 13q involving 13ql4, the second hit must be a local mutation at the RBl gene. It is likely that the mitotic non-disjunction event with loss of the normal chromosome 13 will result in homologous large cytogenetic 13q deletions causing lethality of the cells. …