Summary of molecular genetic testing used in retinoblastoma

Gene symbol	Test method		Mutations detected	Mutation detection frequency by test method*^¶	Test availability^Δ
RB1	Gross deletion/duplication analysis^◊	FISH	Submicroscopic deletions and translocations	>8%	For a list of available laboratories, please see the Genetic Testing Registry
		Heterozygosity testing		8%
		MLPA, quantitative multiplex PCR, other methods^◊	Submicroscopic whole exon(s) deletions, insertions, and rearrangements	16%
	Mutation scanning		Single-base substitutions, small length mutations	70 to 75%
	Sequence analysis (genomic)
	Targeted mutation analysis		Specific panel of recurrent point mutations	25%
	Methylation analysis		Hypermethylation of the promoter region	10 to 12%^§
	Sequence analysis of RNA from blood		(Deep intronic) splice mutations, gross rearrangements	<5%^¥

FISH: fluorescence in situ hybridization; MLPA: multiplex ligation-dependent probe amplification; PCR: polymerase chain reaction; GH: genomic hybridization; CLIA: Clinical Laboratory Improvement Amendments.
* The ability of the test method used to detect a mutation that is present in the indicated gene.
¶ In individuals with normal chromosome studies; refers to the ability to detect a heritable mutation if one is present.
Δ Test availability refers to availability in the GeneTests Laboratory Directory. GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.
◊ Testing that identifies whole-exon deletions/duplications not readily detectable by sequence analysis of genomic DNA; a variety of methods including quantitative PCR, long-range PCR, MLPA, or targeted array GH (gene/segment-specific) may be used. A full array GH analysis that detects deletions/duplications across the genome may also include this gene/segment.
§ In retinoblastoma tumor tissue.
¥ In individuals without a mutation identified by DNA-based analyses.

References:

Lohmann D, Scheffer H, Gaille B. Best practice guidelines for molecular analysis of retinoblastoma. European Molecular Genetics Quality Network 2002.
Rushlow D, Piovesan B, Zhang K, et al. Detection of mosaic RB1 mutations in families with retinoblastoma. Hum Mutat 2009; 30:842.
Zhang K, Nowak I, Rushlow D, et al. Patterns of missplicing caused by RB1 gene mutations in patients with retinoblastoma and association with phenotypic expression. Hum Mutat 2008; 29:475.

Reproduced with permission from: Lohmann DR, Gallie BL. Retinoblastoma. GeneReviews. Pagon RA, Bird TD, Dolan CR, et al (Eds). Copyright © University of Washington, Seattle, 1993-2013. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1452/. Accessed on March 5, 2013.

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Summary of molecular genetic testing used in retinoblastoma