title: Low penetrance of retinoblastoma for p.V654L mutation of the RB1 gene.
abstract: BACKGROUND
  Retinoblastoma is caused by compound heterozygosity or homozygosity of retinoblastoma gene (RB1) mutations. In germline retinoblastoma, mutations in the RB1 gene predispose individuals to increased cancer risks during development. These mutations segregate as autosomal dominant traits with high penetrance (90%).
  
  
  METHODS
  We screened 30 family members from one family using high resolution melting assay and DNA direct sequencing for mutations in the RB1 gene. We evaluate the phenotype and penetrance of germline mutations of the RB1 gene in a large Taiwanese family.
  
  
  RESULTS
  The molecular analysis and clinical details of this family showed phenotypic variability associated with the p.V654L mutation in exon 19 of the RB1 gene in 11 family members. The phenotype varied from asymptomatic to presence of a unilateral tumor. Only four individuals (2 males and 2 females) developed unilateral retinoblastoma, which resulted in calculated low penetrance of 36% (4/11). The four individuals with retinoblastoma were diagnosed before the age of three years. None of their relatives exhibited variable severity or bilateral retinoblastoma.
  
  
  CONCLUSIONS
  The diseased-eye ratio for this family was 0.36, which is lower than current estimates. This suggests that the RB1 p.V654L mutation is a typical mutation associated with low penetrance.
authors: Graduate Institute of Clinical Genomics, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Chia-Cheng
authors: CC
authors: Hung
authors: Shin-Yu
authors: SY
authors: Lin
authors: Chien-Nan
authors: CN
authors: Lee
authors: Chih-Ping
authors: CP
authors: Chen
authors: Shuan-Pei
authors: SP
authors: Lin
authors: Mei-Chyn
authors: MC
authors: Chao
authors: Shyh-Shin
authors: SS
authors: Chiou
authors: Yi-Ning
authors: YN
authors: Su
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