Retinoblastoma: RB1 Gene Sequencing

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Condition Description

Retinoblastoma (RB) is rare malignant tumor of the retina that occurs primarily in infancy and childhood.  Approximately 60% of affected individuals have unilateral RB (affecting one eye) while the remaining 40% have bilateral RB (affecting both eyes).  RB typically presents in the first five years of life; unilateral RB typically occurs at an average age of 24 months and bilateral RB typically occurs at an average age of 15 months. Retinoblastoma occurs in both hereditary and non-hereditary forms.  Virtually all bilateral RB and multifocal RB as well as 15% of unilateral RB is hereditary.  It is estimated that about 55% of all retinoblastoma is hereditary.

Hereditary RB is inherited in an autosomal dominant manner.  Hereditary RB is caused by mutations in the tumor-suppressor gene RB1 located at 13q14.2.  Individuals with hereditary RB are said to have a germline mutation in RB1.  In the majority of hereditary cases, this occurs as a de novo event, however in about 20% of hereditary cases, affected individuals inherit a mutation in RB1 from a parent.  In 90-95% of these patients an RB1 mutation can be detected in their blood.  Individuals with a RB1 mutation have a predisposition to developing RB and other cancers, such as osteosarcomas and pinealoma.

For patients with suspected RB, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.

  • GeneReview
  • Aerts I et al. Retinoblastoma. Orphanet J Rare Diseases. 2006;1:31
  • Nichols KE et al. Recent advances in retinoblastoma genetic research. Curr Opin Ophthalmol. 2009;20(5):351-5.
  • OMIM #614041: RB1 gene
  • OMIM #180200: RB

Genes (1)

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This test is indicated for:
  • Confirmation of a clinical diagnosis of retinoblastoma.


Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient's genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient's gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.


Clinical Sensitivity:  70% of mutations can be identified by sequencing analysis.  Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Analytical Sensitivity: ~99%

Specimen Requirements

When sample fails to meet the acceptable criteria, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (

Submit only 1 of the following specimen types

Preferred specimen type: Whole Blood

Type: Whole Blood

Specimen Requirements:

In EDTA (purple top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva

Specimen Requirements:

OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

  • Deletion/duplication analysis of the RB1 gene by CGH array is available for those individuals in whom sequence analysis is negative.
  • Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
  • Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

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