Boubekeur et al. (2012) conducted a constitutionnal and tumoral RB1 analysis in a group of 21 Algerian patients. Germline abnormalities were found in 2/21 patients of sporadic unilateral retinoblastoma. The spectrum of germline and tumoral alterations included: three nonsense mutations; one mutation affecting splice site; one deletion and two polymorphisms. Two of these mutations are novel and were not previously reported. In two of the patients, Boubekeur et al. (2012) identified mutations in germinal level demonstrating a transmissible form of retinoblastoma.

Shawky et al. (2000) designed a study to detect and define molecular mutations in a sample of 15 Egyptian children (eight males, seven females) with retinoblastoma. In 11 of the cases, the mutation could be identified in one of the seven exons screened. Mutation analysis revealed a tendency for point mutations in some exons of the retinoblastoma gene; exon 14 (mutated in 27% cases), exon 17 and 26 (18% each), and exons 2, 11, 12, and 13 (9% each). These results were in concordance with results in the literature, stating that mutations triggering oncogenesis are distributed throughout many exons in the gene, and that there are no single mutational hotspots in the RB gene. Shawky et al. (2000) interpreted these results to mean that the RB gene product could be exerting multiple regulatory effects mediated by one or more of its domains. Shawky et al. (2000) concluded that such a delineation of mutations would be very helpful in screening programs for families with high risk of retinoblastoma. [Shawky RM, Salem MSZ, Rifaat MM, Ali MA, Zico OAO, Alazeem AA. Molecular mutations of retinoblastoma gene among Egyptian children. Egyptian J Med Hum Genet. 2000; 1(1):83-90.]

In an extension to this study, Shawky et al. (2002) correlated the mutations in these 15 patients with the clinical and inheritance patterns of the disease. Bilaterality of the tumor was observed in 60% of the cases, and unilaterality in the remaining 40%. The 30 parents of these patients were also studied. In 60% of the cases, there was neither positive family history for the disease nor any ophthalmologic evidence of a regressed tumor in the parents, indicating the sporadic nature of inheritance of the disease. However, in 27% of the cases, a positive history of the disease was noted in late siblings, along with an absence of any regressed tumors in the parents, indicating the autosomal recessive nature of inheritance. The remaining 13% cases evidenced autosomal dominant mode of inheritance, by the detection of old, regressed retinoblastomas in the eyes of at least one of the parents. Parental consanguinity was noticed in 53% of the cases; half of them being in sporadic and the rest half in autosomal recessively inherited cases. Genotype-phenotype correlation studies showed that early onset accompanied by rapid progressive course of the disease was seen in patients with mutations in exon 13, whereas later age of onset and a slower course of progression was characteristic of patients with mutations in exon 17. Patients with mutations in exon 2 showed severe rapidly progressive fatal course with multiple tumor foci of both eyes. These results were thought by Shawky et al. (2002) to reflect the importance of the mutated exon in the overall function of the gene product. [Shawky RM, Salem MSZ, Rifaat MM, Alazeem AA. Retinoblastoma gene mutations among Egyptian patients. Egyptian J Med Hum Genet. 2002; 3(1):101-11.]

Ahmad et al. (1999) conducted a mutation analysis of the RB1 gene in a Syrian family showing incomplete penetrance of retinoblastoma. They identified the missense point mutation in exon 21 of the RB1 gene converting a Cys>Arg (codon 712) in one family with a low penetrant phenotype. The proband was unilaterally affected, whereas the paternal uncle was bilaterally affected and the mutation carrier father was unaffected. The T>C substitution abolished a cleavage site for the Nde I restriction enzyme, enabling rapid detection of the mutant allele. Ahmad et al. (1999) suggested that codon 712 may represent a mutational 'hot spot' for the low penetrant phenotypes and that the mutation codes for retinoblastoma protein with an apparently residual tumor-suppressive function give rise to low penetrance.