Low penetrance of retinoblastoma for p.V654L mutation of the RB1 gene
- Equal contributors
1 Graduate Institute of Clinical Genomics, National Taiwan University College of Medicine, Taipei, Taiwan
2 Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
3 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
4 Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
5 Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan
6 Division of Genetics and Metabolism, Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
7 Division of Genetics, Endocrinology and Metabolism, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
8 Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
9 Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
BMC Medical Genetics 2011, 12:76 doi:10.1186/1471-2350-12-76Published: 26 May 2011
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%).
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.
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.
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.