Pathogenic gene screening and phenotypic analysis of six albinism families_Chinese Journal of Ocular Fundus Diseases

Authors：

Li Jie , Xing Yasi , Li Zhanrong , Lu Xiaonan ,  Dai Shuzhen

Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Henan Eye Institute, Henan Eye Hospital, Zhengzhou 450003, China;

Corresponding author：

Dai Shuzhen, Email: dsz997300056@163.com

Keywords：

Albinism, oculocutaneous/genetics; GPR143 gene; Heterozygote; Mutation

DOI：

10.3760/cma.j.issn.1005-1015.2018.06.003

Video：

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ObjectiveTo analyze the pathogenic gene types and phenotypic characteristics of 6 albinism families. Methods A retrospective series of case studies. Six probands of albinism and 20 family members were recruited for this study, 5 probands with clinical manifestations of oculocutaneous albinism (OCA) and 1 proband of ocular albinism (OA). Genomic DNA was extracted from peripheral venous blood which was collected from 6 probands and 20 family members. Genetic variations were screened by whole-exome sequencing or Sanger sequencing and then analyzed the relationship between genotypes and phenotypes. Results Genetic sequencing identified 6 potential pathogenic variants in 4 probands, including 2 compound heterozygous mutations in the 2 genes [TYR (c.1037-7T＞A, c.925_c.926insC), OCA2 (c.2359G＞A, c.587T＞C)] associated with OCA1 and OCA2, and 2 hemizygous mutations in the GPR143[GPR143 (c.11C＞G), GPR143 (c.333G＞A)] associated with OA1, respectively. In which, 5 were novel mutations and confirmed by Sanger sequencing. One case was accorded with OCA in clinical phenotype, but genetic diagnosis was OA1, the others were agreement between clinical diagnosis and genetic diagnosis. Conclusion There are 4 families with mutations in 6 families, representative of 3 type of albinism (OCA1, OCA2, OA1).

Citation： Li Jie, Xing Yasi, Li Zhanrong, Lu Xiaonan, Dai Shuzhen. Pathogenic gene screening and phenotypic analysis of six albinism families. Chinese Journal of Ocular Fundus Diseases, 2018, 34(6): 536-540. doi: 10.3760/cma.j.issn.1005-1015.2018.06.003 Copy

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11.	Simeonov DR, Wang X, Wang C, et al. DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics[J]. Hum Mutat, 2013, 34(6): 827-835. DOI: 10.1002/humu.22315.
12.	Oetting WS, Gardner JM, Fryer JP, et al. Mutations of the human P gene associated with type Ⅱ oculocutaneous albinism (OCA2): mutations in brief no. 205. online[J]. Hum Mutat, 1998, 12(6): 434. DOI:10.1002/(SICI)1098-1004(1998)12:6<434::AID-HUMU16>3.0.CO;2-7.
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16.	Faugere V, Tuffery-Giraud S, Hamel C, et al. Identification of three novel OA1 gene mutations identified in three families misdiagnosed with congenital nystagmus and carrier status determination by real-time quantitative PCR assay[J]. BMC Genet, 2003, 4: 1.
17.	Paavo M, Zhao J, Kim HJ, et al. Mutations in GPR143/OA1 and ABCA4 inform interpretations of short-wavelength and near-infrared fundus autofluorescence[J]. Invest Ophthalmol Vis Sci, 2018, 59(6): 2459-2469. DOI: 10.1167/iovs.18-24213.

1. 李洪义, 郑辉, 吴维青. 白化病相关综合征的遗传与分子发病机制[J]. 国外医学(皮肤性病学分册), 2004, 30(4): 229-231. DOI:10.3760/cma.j.issn.1673-4173.2004.04.010.Li HY, Zheng H, Wu WQ. Molecular genetic mechanism of syndromic forms of albinism[J]. Int J Dermatol Venereol, 2004, 30(4): 229-231. DOI:10.3760/cma.j.issn.1673-4173.2004.04.010.
2. Martinez-Garcia M, Montoliu L. Albinism in Europe[J]. J Dermatol, 2013, 40(5): 319-324. DOI: 10.1111/1346-8138.12170.
3. Oetting WS, King RA. Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism[J]. Hum Mutat, 1999, 13(2): 99-115. DOI: 10.1002/(SICI)1098-1004(1999)13:2<99::AID-HUMU2>3.0.CO;2-C.
4. 魏海云, 李洪义, 郭向明, 等. 白化病的眼表现及其发生机制[J]. 中国实用眼科杂志, 2005, 23(7): 653-656. DOI: 10.3760/cma.j.issn.1006-4443.2005.07.002.Wei HY, Li HY, Guo XM, et al. The manifestations and mechanism of albinism[J]. Chin J Pract Ophthalmol, 2005, 23(7): 653-656. DOI: 10.3760/cma.j.issn.1006-4443.2005.07.002.
5. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. DOI: 10.1038/gim.2015.30.
6. Kamaraj B, Purohit R. Mutational analysis of oculocutaneous albinism: a compact review[J/OL]. Biomed Res Int, 2014, 2014:905472[2014-06-29]. https://dx.doi.org/10.1155/2014/905472. DOI: 10.1155/2014/905472.
7. Montoliu L, Gronskov K, Wei AH, et al. Increasing the complexity: new genes and new types of albinism[J]. Pigment Cell Melanoma Res, 2014, 27(1): 11-18. DOI: 10.1111/pcmr.12167.
8. Qiu B, Ma T, Peng C, et al. Identification of five novel variants in chinese oculocutaneous albinism by targeted next-generation sequencing[J]. Genet Test Mol Biomarkers, 2018, 22(4): 252-258. DOI: 10.1089/gtmb.2017.0211.
9. Hutton SM, Spritz RA. Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type[J]. J Invest Dermatol, 2008, 128(10): 2442-2450. DOI: 10.1038/jid.2008.109.
10. King RA, Pietsch J, Fryer JP, et al. Tyrosinase gene mutations in oculocutaneous albinism 1(OCA1): definition of the phenotype[J]. Hum Genet, 2003, 113(6): 502-513. DOI: 10.1007/s00439-003-0998-1.
11. Simeonov DR, Wang X, Wang C, et al. DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics[J]. Hum Mutat, 2013, 34(6): 827-835. DOI: 10.1002/humu.22315.
12. Oetting WS, Gardner JM, Fryer JP, et al. Mutations of the human P gene associated with type Ⅱ oculocutaneous albinism (OCA2): mutations in brief no. 205. online[J]. Hum Mutat, 1998, 12(6): 434. DOI:10.1002/(SICI)1098-1004(1998)12:6<434::AID-HUMU16>3.0.CO;2-7.
13. Lewis RA. Ocular Albinism, X-Linked[M]. Seattle (WA): University of Washington, 1993.
14. Fang S, Guo X, Jia X, et al. Novel GPR143 mutations and clinical characteristics in six Chinese families with X-linked ocular albinism[J]. Mol Vis, 2008, 14: 1974-1982.
15. 房绍华, 贾小云, 黎仕强, 等. 中国人眼白化病1型的临床特点观察[J]. 中华眼底病杂志, 2012, 28(4): 376-379. DOI:10.3760/cma.j.issn.1005-1015.2012.04.015.Fang SH, Jia XY, Li SQ, et al. Clinical characteristics of ocular albinism type 1 in China[J]. Chin J Ocul Fundus Dis, 2012, 28(4): 376-379. DOI: 10.3760/cma.j.issn.1005-1015.2012.04.015.
16. Faugere V, Tuffery-Giraud S, Hamel C, et al. Identification of three novel OA1 gene mutations identified in three families misdiagnosed with congenital nystagmus and carrier status determination by real-time quantitative PCR assay[J]. BMC Genet, 2003, 4: 1.
17. Paavo M, Zhao J, Kim HJ, et al. Mutations in GPR143/OA1 and ABCA4 inform interpretations of short-wavelength and near-infrared fundus autofluorescence[J]. Invest Ophthalmol Vis Sci, 2018, 59(6): 2459-2469. DOI: 10.1167/iovs.18-24213.

Chinese Journal of Ocular Fundus Diseases

Pathogenic gene screening and phenotypic analysis of six albinism families

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