European Journal of Human Genetics (2011) 19, doi:10.1038/ejhg.2010.200; published online 8 December 20101. DISEASE CHARACTERISTICS1.1 Name of the disease (synonyms)Retinoblastoma.1.2 OMIM# of the disease180200.1.3 Name of the analysed genes or DNA/chromosome segmentsRB1.1.4 OMIM# of the gene(s)180200.1.5 Mutational spectrumGermline mutations: point mutations, deletions, insertions. Somaticmutations (tumour only): point mutations, deletions, insertions,epigenetic silencing (somatic), chromosomal rearrangements (somaticloss of heterozygosity).1.6 Analytical methodsChromosome analysis, FISH, sequence analysis, MLPA/quantitativemultiplex PCR, testing for loss of heterozygosity, methylation analysis.Addendum:(1) RB1 testing is proposed for all patients with a retinoblastomadiagnosis irrespective of the nature at the time of presentation(unilateral, bilateral, sporadic, familial).(2) In patients with retinoblastoma who also present withdysmorphic features and/or developmental delay chromosomalanalysis, FISH or array CGH analysis is performed first.(3) If tumour tissue is available, the aim is to determine themutations that inactivate the two RB1 alleles (either two somaticmutations or one somatic mutation and a germline mutation).Analytical methods for the study of DNA from tumours includesequence analysis, MLPA/quantitative multiplex PCR, testing for lossof heterozygosity and methylation analysis.Following identification of the mutations that inactivate the twoRB1 alleles, constitutionalDNA (forexample,extractedfromblood) istested for the presence of these mutations.(4) If no tumour tissue is available, the aim is to determine amutation that inactivates one of the two RB1 alleles. Analyticalmethods for the study of DNA from blood include sequence analysisand MLPA/quantitative multiplex PCR.(5) Mutational mosaicism is not uncommon in patients withisolated (sporadic) retinoblastoma. Methods for mutation detectionin DNA from blood must be sensitive enough to permit the detectionof mutant alleles present in only a fraction of the DNA analysed.1.7 Analytical validationIn some cases (for example, single-exon deletions detected by MLPA),the results of semiquantitative methods should be confirmed by anindependent technique (long-range PCR – sequencing, RNA analysis,segregation of genetic variation).1.8 Estimated frequency of the disease(incidence at birth (‘birth prevalence’) or population prevalence)Prevalence of retinoblastoma: 1/15 000 to 1/20 000 (40% bilateral,60% unilateral).Hereditary retinoblastoma susceptibility present in 50% of patients(all familial cases, almost all sporadic bilateral cases, and 13% ofunilateral cases).1.9 If applicable, prevalence in the ethnic group of the investigatedpersonNot applicable.1.10 Diagnostic settingComment:Not applicable.2. TEST CHARACTERISTICS