Identification of a novel idiopathic congenital nystagmus‑causing missense mutation, p.G296C, in the FRMD7 gene

Xiu,Yanghui; Yao,Yihua; Yang,Tanchu; Pan,Meihua; Yang,Hui; Fang,Weifang; Gu,Feng; Zhao,Junzhao; Zhu,Yihua

doi:10.3892/mmr.2018.9260

Identification of a novel idiopathic congenital nystagmus‑causing missense mutation, p.G296C, in the FRMD7 gene

Authors:
- Yanghui Xiu
- Yihua Yao
- Tanchu Yang
- Meihua Pan
- Hui Yang
- Weifang Fang
- Feng Gu
- Junzhao Zhao
- Yihua Zhu
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Affiliations: The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Eye Institute and Xiamen Eye Center Affiliated Xiamen University, Xiamen, Fujian 361001, P.R. China, Department of Ophthalmology, Xiamen Children's Hospital, Xiamen, Fujian 361000, P.R. China, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027, P.R. China, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: July 9, 2018 https://doi.org/10.3892/mmr.2018.9260
Pages: 2816-2822
Copyright: © Xiu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Exploring the genetic basis for idiopathic congenital nystagmus is critical for improving our understanding of its molecular pathogenesis. In the present study, direct sequencing using gene specific primers was performed in order to identify the causative mutations in two brothers from a Chinese family who had been diagnosed with idiopathic congenital nystagmus. A comprehensive ophthalmological examination, including eye movement recordings, fundus examination, and retinal optical coherence tomography imaging was also conducted, to characterize the disease phenotype. The results revealed that the two brothers exhibited clear signs of nystagmus without any other ocular anomalies. Direct sequencing revealed a G to T transition (c.886G>T) in exon 9 of the four‑point‑one, ezrin, radixin, moesin domain‑containing 7 (FRMD7) gene, which resulted in a conservative substitution of glycine to cysteine at codon 296 (p.G296C), leading to idiopathic congenital nystagmus in the two affected brothers. c.886G>T is a novel idiopathic congenital nystagmus‑inducing mutation in the FRMD7 gene. This finding expands the spectrum of known gene mutations in idiopathic congenital nystagmus, and may be useful for faster gene diagnosis, prenatal testing, the development of potential gene therapies, and for improving the understanding of the molecular pathogenesis of idiopathic congenital nystagmus.

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1	Tarpey P, Thomas S, Sarvananthan N, Mallya U, Lisgo S, Talbot CJ, Roberts EO, Awan M, Surendran M, McLean RJ, et al: Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus. Nat Genet. 38:1242–1244. 2006. View Article : Google Scholar : PubMed/NCBI
2	Serra A, Dell'Osso LF, Jacobs JB and Burnstine RA: Combined gaze-angle and vergence variation in infantile nystagmus: Two therapies that improve the high-visual-acuity field and methods to measure it. Invest Ophthalmol Vis Sci. 47:2451–2460. 2006. View Article : Google Scholar : PubMed/NCBI
3	Balzer BWR, Catt CJ, Bou-Abdou M and Martin FJ: Visual acuity improves in children and adolescents with idiopathic infantile nystagmus. Asia Pac J Ophthalmol (Phila). 7:99–101. 2018.PubMed/NCBI
4	Kerrison JB, Arnould VJ, Barmada MM, Koenekoop RK, Schmeckpeper BJ and Maumenee IH: A gene for autosomal dominant congenital nystagmus localizes to 6p12. Genomics. 33:523–526. 1996. View Article : Google Scholar : PubMed/NCBI
5	Zhu Y, Zhuang J, Ge X, Zhang X, Wang Z, Sun J, Yang J and Gu F: Identifcation of a novel mutation p.I240T in the FRMD7 gene in a family with congenital nystagmus. Sci Rep. 3:30842013. View Article : Google Scholar : PubMed/NCBI
6	Cabot A, Rozet JM, Gerber S, Perrault I, Ducroq D, Smahi A, Souied E, Munnich A and Kaplan J: A gene for X-linked idiopathic congenital nystagmus (NYS1) maps to chromosome xp11.4-p11.3. Am J Hum Genet. 64:1141–1146. 1999. View Article : Google Scholar : PubMed/NCBI
7	Bassi MT, Schiaffino MV, Renieri A, De Nigris F, Galli L, Bruttini M, Gebbia M, Bergen AA, Lewis RA and Ballabio A: Cloning of the gene for ocular albinism type-1 from the distal short arm of the × chromosome. Nat Genet. 10:13–19. 1995. View Article : Google Scholar : PubMed/NCBI
8	Kerrison JB, Vagefi MR, Barmada MM and Maumenee LH: Congenital motor nystagmus linked to xq26-q27. Am J Hum Genet. 64:600–607. 1999. View Article : Google Scholar : PubMed/NCBI
9	Watkins RJ, Thomas MG, Talbot CJ, Gottlob I and Shackleton S: The role of FRMD7 in idiopathic infantile nystagmus. J Ophthalmol. 2012:4609562012. View Article : Google Scholar : PubMed/NCBI
10	Bai D, Shi W, Qi Z, Li W, Wei A, Cui Y, Li C and Li L: Clinical feature and waveform in infantile nystagmus syndrome in children with FRMD7 gene mutations. Sci China Life Sci. 60:707–713. 2017. View Article : Google Scholar : PubMed/NCBI
11	Jia X, Zhu X, Li Q, Jia X, Li S and Guo X: Novel mutations of FRMD7 in chinese patients with congenital motor nystagmus. Mol Med Rep. 16:1753–1758. 2017. View Article : Google Scholar : PubMed/NCBI
12	Gupta S, Pathak E, Chaudhry VN, Chaudhry P, Mishra R, Chandra A, Mukherjee A and Mutsuddi M: A novel mutation in FRMD7 causes X-linked idiopathic congenital nystagmus in a north indian family. Neurosci Lett. 597:170–175. 2015. View Article : Google Scholar : PubMed/NCBI
13	Li N, Wang X, Wang Y, Wang L, Ying M, Han R, Liu Y and Zhao K: Investigation of the gene mutations in two chinese families with X-linked infantile nystagmus. Mol Vis. 17:461–468. 2011.PubMed/NCBI
14	Liu Z, Mao S, Pu J, Ding Y, Zhang B and Ding M: A novel missense mutation in the FERM domain containing 7 (FRMD7) gene causing X-linked idiopathic congenital nystagmus in a chinese family. Mol Vis. 19:1834–1840. 2013.PubMed/NCBI
15	Al-Moallem B, Bauwens M, Walraedt S, Delbeke P, De Zaeytijd J, Kestelyn P, Meire F, Janssens S, van Cauwenbergh C, Verdin H, et al: Novel FRMD7 mutations and genomic rearrangement expand the molecular pathogenesis of X-linked idiopathic infantile nystagmus. Invest Ophthalmol Vis Sci. 56:1701–1710. 2015. View Article : Google Scholar : PubMed/NCBI
16	Thomas S, Proudlock FA, Sarvananthan N, Roberts EO, Awan M, McLean R, Surendran M, Kumar AS, Farooq SJ, Degg C, et al: Phenotypical characteristics of idiopathic infantile nystagmus with and without mutations in FRMD7. Brain. 131:1259–1267. 2008. View Article : Google Scholar : PubMed/NCBI
17	Kohmoto T, Okamoto N, Satomura S, Naruto T, Komori T, Hashimoto T and Imoto I: A FRMD7 variant in a japanese family causes congenital nystagmus. Hum Genome Var. 2:150022015. View Article : Google Scholar : PubMed/NCBI
18	Radhakrishna U, Ratnamala U, Deutsch S, Bartoloni L, Kuracha MR, Singh R, Banwait J, Bastola DK, Johar K, Nath SK and Antonarakis SE: Novel homozygous, heterozygous and hemizygous FRMD7 gene mutations segregated in the same consanguineous family with congenital X-linked nystagmus. Eur J Hum Genet. 20:1032–1036. 2012. View Article : Google Scholar : PubMed/NCBI
19	Choi JH, Shin JH, Seo JH, Jung JH and Choi KD: A start codon mutation of the FRMD7 gene in two korean families with idiopathic infantile nystagmus. Sci Rep. 5:130032015. View Article : Google Scholar : PubMed/NCBI
20	Zhao H, Huang XF, Zheng ZL, Deng WL, Lei XL, Xing DJ, Ye L, Xu SZ, Chen J, Zhang F, et al: Molecular genetic analysis of patients with sporadic and X-linked infantile nystagmus. BMJ Open. 6:e0106492016. View Article : Google Scholar : PubMed/NCBI
21	He X, Gu F, Wang Z, Wang C, Tong Y, Wang Y, Yang J, Liu W, Zhang M and Ma X: A novel frameshift mutation in FRMD7 causing X-linked idiopathic congenital nystagmus. Genet Test. 12:607–613. 2008. View Article : Google Scholar : PubMed/NCBI
22	Hu Y, Shen J, Zhang S, Yang T, Huang S and Yuan H: A novel splicing mutation of the FRMD7 gene in a Chinese family with X-linked congenital nystagmus. Mol Vis. 18:87–91. 2012.PubMed/NCBI
23	Hu J, Liang D, Xue J, Liu J and Wu L: A novel GPR143 splicing mutation in a Chinese family with X-linked congenital nystagmus. Mol Vis. 17:715–722. 2011.PubMed/NCBI
24	Du W, Bu J, Dong JM, Jia Y, Li J, Liang C, Si S and Wang L: A novel frame-shift mutation in FRMD7 causes X-linked idiopathic congenital nystagmus in a Chinese family. Mol Vis. 17:2765–2768. 2011.PubMed/NCBI
25	Schorderet DF, Tiab L, Gaillard MC, Lorenz B, Klainguti G, Kerrison JB, Traboulsi EI and Munier FL: Novel mutations in FRMD7 in X-linked congenital nystagmus. Mutation in brief #963. Online. Hum Mutat. 28:5252007. View Article : Google Scholar : PubMed/NCBI
26	Li N, Wang L, Cui L, Zhang L, Dai S, Li H, Chen X, Zhu L, Hejtmancik JF and Zhao K: Five novel mutations of the FRMD7 gene in Chinese families with X-linked infantile nystagmus. Mol Vis. 14:733–738. 2008.PubMed/NCBI
27	Nash DL, Diehl NN and Mohney BG: Incidence and types of pediatric nystagmus. Am J Ophthalmol. 182:31–34. 2017. View Article : Google Scholar : PubMed/NCBI
28	Sarvananthan N, Surendran M, Roberts EO, Jain S, Thomas S, Shah N, Proudlock FA, Thompson JR, McLean RJ, Degg C, et al: The prevalence of nystagmus: The leicestershire nystagmus survey. Invest Ophthalmol Vis Sci. 50:5201–5206. 2009. View Article : Google Scholar : PubMed/NCBI
29	Penix K, Swanson MW and DeCarlo DK: Nystagmus in pediatric patients: Interventions and patient-focused perspectives. Clin Ophthalmol. 9:1527–1536. 2015.PubMed/NCBI
30	Holmström G, Bondeson ML, Eriksson U, Åkerblom H and Larsson E: ‘Congenital’ nystagmus may hide various ophthalmic diagnoses. Acta Ophthalmol. 92:412–416. 2014. View Article : Google Scholar : PubMed/NCBI
31	Thomas MG, Maconachie G, Sheth V, McLean RJ and Gottlob I: Development and clinical utility of a novel diagnostic nystagmus gene panel using targeted next-generation sequencing. Eur J Hum Genet. 25:725–734. 2017. View Article : Google Scholar : PubMed/NCBI
32	Clement RA, Whittle JP, Muldoon MR, Abadi RV, Broomhead DS and Akman O: Characterisation of congenital nystagmus waveforms in terms of periodic orbits. Vision Res. 42:2123–2130. 2002. View Article : Google Scholar : PubMed/NCBI