Splicing aberrations caused by constitutional RB1 gene mutations in retinoblastoma.
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Date
2011-06
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Abstract
Analysis of RB1 mRNA from blood leukocytes of patients with retinoblastoma identified the effects of mutations
involving consensus splice site, exonic substitution and whole-exon deletions identified in genomic DNA of these
patients. In addition, this study identified mutations in cases in which no mutations were detectable in the genomic
DNA. One proband had mutation at the canonical splice site at +5 position of IVS22, and analysis of the transcripts
in this family revealed skipping of exon 22 in three members of this family. In one proband, a missense substitution
of c.652T>G (g.56897T>G; Leu218Val) in exon 7 led to splicing aberrations involving deletions of exons 7 and 8,
suggesting the formation of a cryptic splice site. In two probands with no detectable changes in the genomic DNA
upon screening of RB1 exons and flanking intronic sequences, transcripts were found to have deletions of exon 6 in
one, and exons 21 and 22 in another family. In two probands, RNA analysis confirmed genomic deletions involving
one or more exons. This study reveals novel effects of RB1 mutations on splicing and suggests the utility of RNA
analysis as an adjunct to mutational screening of genomic DNA in retinoblastoma.
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Keywords
Mutations, RB1, retinoblastoma, RT-PCR, splicing defects, transcript analysis
Citation
Parsam Vidya Latha, Ali Mohammed Javed, Honavar Santosh G, Vemuganti Geeta K, Kannabiran Chitra. Splicing aberrations caused by constitutional RB1 gene mutations in retinoblastoma. Journal of Biosciences. 2011 Jun; 36(2): 281-287.