Analysis of gene mutation in a Chinese family with low penetrance retinoblastoma_Chinese Journal of Ocular Fundus Diseases

Authors：

XueKang , WuJihong , RenHui , 张锐 ,  钱江

Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai 200031, China;

Corresponding author：

钱江, Email: qianjiang58@126.com

Keywords：

Retinoblastoma; Genes, neoplasm; Penetrance; High-throughput nucleotide sequencing

DOI：

10.3760/cma.j.issn.1005-1015.2015.06.010

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To identify the pathogenic mutation in a three generation Chinese family with low penetrance retinoblastoma (RB). Methods 8 from 9 family members received complete ophthalmic examinations. DNA was extracted from 6 family members. Using exon combined target region capture sequencing chip to screen the candidate disease-causing mutations. Sanger sequencing were used to confirm the disease-causing mutation. Results Among 9 family members, the proband (Ⅲ2) was bilateral RB, Ⅲ1 was unilateral RB, Ⅲ3 was dead for bilateral RB. Normal fundus were observed in the left eye ofⅢ1 and the eyes of other family members except the proband. Sequence analysis of RB1 gene revealed a missense mutation c.1981C > T (p.Arg661Trp) in the proband and two carriers (Ⅱ2, Ⅱ3), but not in the two normal subjects (Ⅱ1, Ⅱ4). We suspect that the RB penetrance in the family was 50%. Conclusions There is a missense mutation c.1981C > T in a Chinese family with low penetrance RB. The RB penetrance is 50%.

Citation： XueKang, WuJihong, RenHui. Analysis of gene mutation in a Chinese family with low penetrance retinoblastoma. Chinese Journal of Ocular Fundus Diseases, 2015, 31(6): 553-555. doi: 10.3760/cma.j.issn.1005-1015.2015.06.010 Copy

1.	Knudson AG Jr. Mutation and cancer:statistical study of retinoblastoma[J].Proc Natl Acad Sci USA, 1971, 68(4):820-823.
2.	Lohmann DR, Gallie BL.Retinoblastoma:revisiting the model prototype of inherited cancer[J]. Am J Genet C Semin Med Genet, 2004, 129C(1):23-28.
3.	van Dijk EL, Auger H, Jaszczyszyn Y, et al.Ten years of next-generation sequencing technology[J].Trends Genet, 2014, 30(9):418-426.
4.	Lin E, Chien J, Ong FS, et al.Challenges and opportunities for next-generation sequencing in companion diagnostics[J]. Expert Rev Mol Diagn, 2015, 15(2):193-209.
5.	Kuhlenbäumer G, Hullmann J, Appenzeller S. Novel genomic techniques open new avenues in the analysis of monogenic disorders[J]. Hum Mutat, 2011, 32(2):144-151.
6.	Marees T, Moll AC, Imhof SM, et al.Risk of second malignancies in survivors of retinoblastoma:more than 40 years of follow-up[J].J Nat Cancer Inst, 2008, 100(24):1771-1779.
7.	Shields CL, Shelil A, Cater J, et al. Development of new retinoblastomas following six cycles of chemoreduction for retinoblastoma in 162 eyes of 106 consecutive patients[J]. Arch Opthalmol, 2003, 121(11):1571-1576.
8.	Onadim Z, Hogg A, Baird P N, et al.Oncogenic point mutations in exon 20 of the RB1 gene in families showing incomplete penetrance and mild expression of the retinoblastoma phenotype[J].Proc Natl Acad Sci USA, 1992, 89(13):6177-6181.
9.	Abouzeid H, Munier FL, Thonney F, et al. Ten novel RB1 gene mutations in patients with retinoblastoma[J].Mol Vis, 2007, 13:1740-1745.
10.	Otterson GA, Modi S, Nguyen Ket al.Temperature-sensitive RB mutations linked to incomplete penetrance of familial retinoblastoma in 12 families[J].Am J Hum Genet, 1999, 65(4):1040-1046.
11.	杜琴, 江悦华, Brenda L.Gallie.Rb1基因第24和25外显子缺失导致低外显性视网膜母细胞瘤[J].中华医学遗传学杂志, 2002, 19(5):370-374.
12.	Castera L, Sabbagh A, Dehainault C, et al.MDM2 as a modifier gene in refinoblastoma[J].J Natl Cancer Inst, 20l0, 102(23):1805-1808.
13.	Rushlow D, Piovesan B, Zhang K, et al. Detection of mosaic RB1 mutations in families with retinoblastoma[J]. Hum Mutat, 2009, 30(5):842-851.
14.	何明燕, 安宇, 李刚, 等.儿童视网膜母细胞瘤患者RB1基因胚系突变的特征分析[J].中华医学遗传学杂志, 2013, 30(5):509-512.

1. Knudson AG Jr. Mutation and cancer:statistical study of retinoblastoma[J].Proc Natl Acad Sci USA, 1971, 68(4):820-823.
2. Lohmann DR, Gallie BL.Retinoblastoma:revisiting the model prototype of inherited cancer[J]. Am J Genet C Semin Med Genet, 2004, 129C(1):23-28.
3. van Dijk EL, Auger H, Jaszczyszyn Y, et al.Ten years of next-generation sequencing technology[J].Trends Genet, 2014, 30(9):418-426.
4. Lin E, Chien J, Ong FS, et al.Challenges and opportunities for next-generation sequencing in companion diagnostics[J]. Expert Rev Mol Diagn, 2015, 15(2):193-209.
5. Kuhlenbäumer G, Hullmann J, Appenzeller S. Novel genomic techniques open new avenues in the analysis of monogenic disorders[J]. Hum Mutat, 2011, 32(2):144-151.
6. Marees T, Moll AC, Imhof SM, et al.Risk of second malignancies in survivors of retinoblastoma:more than 40 years of follow-up[J].J Nat Cancer Inst, 2008, 100(24):1771-1779.
7. Shields CL, Shelil A, Cater J, et al. Development of new retinoblastomas following six cycles of chemoreduction for retinoblastoma in 162 eyes of 106 consecutive patients[J]. Arch Opthalmol, 2003, 121(11):1571-1576.
8. Onadim Z, Hogg A, Baird P N, et al.Oncogenic point mutations in exon 20 of the RB1 gene in families showing incomplete penetrance and mild expression of the retinoblastoma phenotype[J].Proc Natl Acad Sci USA, 1992, 89(13):6177-6181.
9. Abouzeid H, Munier FL, Thonney F, et al. Ten novel RB1 gene mutations in patients with retinoblastoma[J].Mol Vis, 2007, 13:1740-1745.
10. Otterson GA, Modi S, Nguyen Ket al.Temperature-sensitive RB mutations linked to incomplete penetrance of familial retinoblastoma in 12 families[J].Am J Hum Genet, 1999, 65(4):1040-1046.
11. 杜琴, 江悦华, Brenda L.Gallie.Rb1基因第24和25外显子缺失导致低外显性视网膜母细胞瘤[J].中华医学遗传学杂志, 2002, 19(5):370-374.
12. Castera L, Sabbagh A, Dehainault C, et al.MDM2 as a modifier gene in refinoblastoma[J].J Natl Cancer Inst, 20l0, 102(23):1805-1808.
13. Rushlow D, Piovesan B, Zhang K, et al. Detection of mosaic RB1 mutations in families with retinoblastoma[J]. Hum Mutat, 2009, 30(5):842-851.
14. 何明燕, 安宇, 李刚, 等.儿童视网膜母细胞瘤患者RB1基因胚系突变的特征分析[J].中华医学遗传学杂志, 2013, 30(5):509-512.

Chinese Journal of Ocular Fundus Diseases

Analysis of gene mutation in a Chinese family with low penetrance retinoblastoma

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content