A novel mutation Gly109Val in the RS1 gene of X-linked juvenile retinoschisis in a Chinese family_Chinese Journal of Ocular Fundus Diseases

Authors：

ZhangJunyan , YangXiufen , GuHong , 徐军 , 刘宁朴 ,  马凯

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing 100730, China;

Corresponding author：

马凯, Email: makain@163.com

Keywords：

Retinoschisis/genetics; DNA mutational analysis; Mutation

DOI：

10.3760/cma.j.issn.1005-1015.2014.01.016

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To report the clinical findings and RS1 gene mutation analysis of a Chinese family with X-linked juvenile retinoschisis (XLRS). Methods The pedigree of this XLRS family was studied. Nine individuals (10 eyes of 6 males, 6 eyes of 3 females), including the proband, received ocular examination, fundus photography and optical coherence tomography (OCT). Direct DNA sequencing of the 6 exons of RS1 gene was used to detect the RS1 mutation in 12 family members. Results The present pedigree included 15 members of three generations. Among them, 5 male members were diagnosed with XLRS. The retina of other 4 family members were normal, including 1 male (2 eyes) and 3 females (6 eyes). Visual acuity of these 5 patients ranged from hand movement to 0.5 and both eyes of them were involved. The age when visual acuity begins to decrease was all less than 10 years. Fundus color photographic examination showed macular radial cystoid retinoschisis and retinoschisis of the peripheral retina. OCT images showed retinoschisis in macular regions (8 eyes) or peripheral retina (6 eyes). Genetic testing showed that 1 male had no mutation in RS1 gene (p.Gly109Val). All 5 patients had a point mutation (c.326G>T) at exon 4 of RS1 gene, which cause the 109th amino acid changed from glycine to valine in the RS1 protein. A 3-year-old kid also had this mutation. The 3 females with normal retina had heterozygous mutations of Gly109Val, so they are the mutation carriers. Conclusion The novel p.Gly109Val mutation is the causing mutation in this Chinese family with X-linked juvenile retinoschisis.

Citation： ZhangJunyan, YangXiufen, GuHong. A novel mutation Gly109Val in the RS1 gene of X-linked juvenile retinoschisis in a Chinese family. Chinese Journal of Ocular Fundus Diseases, 2014, 30(1): 62-65. doi: 10.3760/cma.j.issn.1005-1015.2014.01.016 Copy

1.	The Retinoschisis Consortium.Functional implications of the spectrum of mutations found in 234 cases with X-linked juvenile retinoschisis[J]. Hum Mol Genet,1998,7:1185-1192.
2.	Sauer CG, Gehrig A, Warneke-Wittstock R, et al.Positional cloning of the gene associated with X-linked juvenile retinoschisis[J]. Nat Genet,1997,17:164-170.
3.	马翔, 黎晓新, 赵贵阳.先天性视网膜劈裂症基因突变型与临床表现型的关系[J]. 中华实验眼科杂志,2011,29:367-372.
4.	Hayashi T, Omoto S, Takeuchi T,et al.Four Japanese male patients with juvenile retinoschisis:only three have mutations in the RS1 gene[J]. Am J Ophthalmol, 2004,138:788-798.
5.	Vincent A, Robson AG, Neveu MM,et al.A Phenotype-genotype correlation study of X-linked Retinoschisis[J].Ophthalmology,2013,120:1454-1464.
6.	Saldana M, Thompson J, Monk E, et al.X-linked retinoschisis in a female with a heterozygous RS1 missense mutation[J]. Am J Med Genet A,2007, 143:608-609.
7.	Gehrig A, White K, Lorenz B, et al.Assessment of RS1 in X-linked juvenile retinoschisis and sporadic senile retinoschisis[J]. Clin Genet,1999,55:461-465.
8.	Tsang SH, Vaclavik V, Bird AC,et al.Novel phenotypic and genotypic findings in X-linked Retinoschisis[J]. Arch Ophthalmol,2007,125:259-267.
9.	Inoue Y, Yamamoto S, Okada M,et al.X-linked retinoschisis with point mutations in the XLRS1 gene[J]. Arch Ophthalmol,2000,118:93-96.
10.	Hiriyanna KT, Bingham EL, Yashar BM, et al.Novel mutations in XLRS1 causing retinoschisis, including first evidence of putative leader sequence change[J]. Hum Mutat,1999,14:423-427.
11.	Molday LL, Hicks D, Sauer CG,et al.Expression of X-linked retinoschisis protein RS1 in photoreceptor and bipolar cells[J]. Invest Ophthalmol Vis Sci,2001,42:816-825.
12.	Takada Y, Fariss RN, Muller M,et al.Retinoschisin expression and localization in rodent and human pineal and consequences of mouse RS1 gene knockout[J]. Mol Vis,2006,12:1108-1116.
13.	Molday RS.Focus on molecules:retinoschisin (RS1)[J]. Exp Eye Res,2007,84:227-228.
14.	Grayson C, Reid SN, Ellis JA,et al.Retinoschisin, the X-linked retinoschisis protein, is a secreted photoreceptor protein, and is expressed and released by Weri-Rb1 cells[J]. Hum Mol Genet,2000,9:1873-1879.
15.	Wu WW, Wong JP, Kast J,et al.RS1, a discoidin domain-containing retinal cell adhesion protein associated with X-linked retinoschisis, exists as a novel disulfide-linked octamer[J]. J Biol Chem,2005,280:10721-10730.
16.	Molday RS, Kellner U, Weber BH.X-linked juvenile retinoschisis:clinical diagnosis, genetic analysis, and molecular mechanisms[J]. Prog Retin Eye Res,2012,31:195-212.
17.	Wang T, Waters CT, Rothman AM,et al.Intracellular retention of mutant retinoschisin is the pathological mechanism underlying X-linked retinoschisis[J].Hum Mol Genet,2002, 11:3097-3105.
18.	Wu WW, Molday RS.Defective discoidin domain structure, subunit assembly, and endoplasmic reticulum processing of retinoschisin are primary mechanisms responsible for X-linked Retinoschisis[J]. J Biol Chem,2003,278:28139-28146.

1. The Retinoschisis Consortium.Functional implications of the spectrum of mutations found in 234 cases with X-linked juvenile retinoschisis[J]. Hum Mol Genet,1998,7:1185-1192.
2. Sauer CG, Gehrig A, Warneke-Wittstock R, et al.Positional cloning of the gene associated with X-linked juvenile retinoschisis[J]. Nat Genet,1997,17:164-170.
3. 马翔, 黎晓新, 赵贵阳.先天性视网膜劈裂症基因突变型与临床表现型的关系[J]. 中华实验眼科杂志,2011,29:367-372.
4. Hayashi T, Omoto S, Takeuchi T,et al.Four Japanese male patients with juvenile retinoschisis:only three have mutations in the RS1 gene[J]. Am J Ophthalmol, 2004,138:788-798.
5. Vincent A, Robson AG, Neveu MM,et al.A Phenotype-genotype correlation study of X-linked Retinoschisis[J].Ophthalmology,2013,120:1454-1464.
6. Saldana M, Thompson J, Monk E, et al.X-linked retinoschisis in a female with a heterozygous RS1 missense mutation[J]. Am J Med Genet A,2007, 143:608-609.
7. Gehrig A, White K, Lorenz B, et al.Assessment of RS1 in X-linked juvenile retinoschisis and sporadic senile retinoschisis[J]. Clin Genet,1999,55:461-465.
8. Tsang SH, Vaclavik V, Bird AC,et al.Novel phenotypic and genotypic findings in X-linked Retinoschisis[J]. Arch Ophthalmol,2007,125:259-267.
9. Inoue Y, Yamamoto S, Okada M,et al.X-linked retinoschisis with point mutations in the XLRS1 gene[J]. Arch Ophthalmol,2000,118:93-96.
10. Hiriyanna KT, Bingham EL, Yashar BM, et al.Novel mutations in XLRS1 causing retinoschisis, including first evidence of putative leader sequence change[J]. Hum Mutat,1999,14:423-427.
11. Molday LL, Hicks D, Sauer CG,et al.Expression of X-linked retinoschisis protein RS1 in photoreceptor and bipolar cells[J]. Invest Ophthalmol Vis Sci,2001,42:816-825.
12. Takada Y, Fariss RN, Muller M,et al.Retinoschisin expression and localization in rodent and human pineal and consequences of mouse RS1 gene knockout[J]. Mol Vis,2006,12:1108-1116.
13. Molday RS.Focus on molecules:retinoschisin (RS1)[J]. Exp Eye Res,2007,84:227-228.
14. Grayson C, Reid SN, Ellis JA,et al.Retinoschisin, the X-linked retinoschisis protein, is a secreted photoreceptor protein, and is expressed and released by Weri-Rb1 cells[J]. Hum Mol Genet,2000,9:1873-1879.
15. Wu WW, Wong JP, Kast J,et al.RS1, a discoidin domain-containing retinal cell adhesion protein associated with X-linked retinoschisis, exists as a novel disulfide-linked octamer[J]. J Biol Chem,2005,280:10721-10730.
16. Molday RS, Kellner U, Weber BH.X-linked juvenile retinoschisis:clinical diagnosis, genetic analysis, and molecular mechanisms[J]. Prog Retin Eye Res,2012,31:195-212.
17. Wang T, Waters CT, Rothman AM,et al.Intracellular retention of mutant retinoschisin is the pathological mechanism underlying X-linked retinoschisis[J].Hum Mol Genet,2002, 11:3097-3105.
18. Wu WW, Molday RS.Defective discoidin domain structure, subunit assembly, and endoplasmic reticulum processing of retinoschisin are primary mechanisms responsible for X-linked Retinoschisis[J]. J Biol Chem,2003,278:28139-28146.

Chinese Journal of Ocular Fundus Diseases

A novel mutation Gly109Val in the RS1 gene of X-linked juvenile retinoschisis in a Chinese family

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content