title: Mutation detection and genetic counseling in retinoblastoma using heteroduplex analysis.
abstract: Gene diagnosis is essential for confident presymptomatic prediction, genetic counseling, and early management of hereditary retinoblastoma. In screening the leukocyte DNA of three patients with bilateral retinoblastoma for RB1-gene heterozygous germline mutations, we identified mutations involving exon 3 or 18 of the RB1 gene by using heteroduplex analysis and sequencing. In one case the mutation was a 2 bp GT deletion resulting in the loss of the exon 18 splicing-donor; another mutation was a G-to-T transversion at codon 580 in exon 18, which converts Arg to a stop codon. The third mutation involved in 1 bp deletion at codon 96 in exon 3, which leads to a premature stop codon at codon 110. We used information from this heteroduplex technique for genetic counseling and presymptomatic prediction. A newborn was identified as normal, using gene diagnosis; his 15-month follow-up confirmed our prediction.
authors.affiliation: Department of Ophthalmology, Teikyo University Ichihara Hospital, Chiba, Japan.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Minoda
mesh_terms: D001483:Base Sequence; D005091:Exons; D005134:Eye Neoplasms / Q000235:genetics*; D005260:Female; D005544:Forecasting; D005817:Genetic Counseling; D006801:Humans; D007223:Infant; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009692:Nucleic Acid Heteroduplexes / Q000032:analysis; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012175:Retinoblastoma / Q000235:genetics*
chemical_list: D015335:Molecular Probes; D009692:Nucleic Acid Heteroduplexes