A Disease-Causing FRMD7 Variant in a Chinese Family with Infantile Nystagmus
- 39 Downloads
In this report, we described a large Han-Chinese family which presents with various phenotypes from unaffected to manifested nystagmus in females. Infantile nystagmus (IN) is characterized by bilateral, involuntary, and periodic eyeball oscillation, occurring at birth or within the first 6 months. The most common inheritance pattern of IN is an X-linked form with incomplete penetrance among females, and the FERM domain containing 7 gene (FRMD7) is a main disease-causing gene. A combination of exome sequencing and Sanger sequencing, as well as detailed clinical examinations were performed on the Chinese IN family. An FRMD7 c.47T>C (p.Phe16Ser) variant was proposed as the disease-causing variant. Incomplete penetrance was found in females with the FRMD7 c.47T>C variant, and hemizygous male affected subjects presented more severe manifestations compared to heterozygous female affected subjects. These findings could enhance genetic counseling and antenatal diagnosis of IN.
KeywordsInfantile nystagmus FERM domain containing 7 Disease-causing variant Phenotype difference
We thank the participating members and investigators for their cooperation and efforts in collecting the genetic information, clinical data, and DNA specimens.
This work was supported by the National Natural Science Foundation of China [81670216, 81800219, and 81873686], Natural Science Foundation of Hunan Province [2016JJ2166 and 2018JJ2660], Scientific Research Project of Health and Family Planning Commission of Hunan Province, China [B20180729, B20180760 and B20180834], and National-level College Students’ Innovative Training Plan Program, China .
Compliance with Ethical Standards
The study adhered to the tenets of the Declaration of Helsinki. The research protocol was approved by the Institutional Review Board of the Third Xiangya Hospital, Central South University (Changsha, China). All participants and their guardians have signed the written informed consent.
Conflict of Interest
The authors declare that they have no conflict of interest.
- AlMoallem B, Bauwens M, Walraedt S, Delbeke P, De Zaeytijd J, Kestelyn P, Meire F, Janssens S, van Cauwenbergh C, Verdin H, Hooghe S, Kumar Thakur P, Coppieters F, De Leeneer K, Devriendt K, Leroy BP, De Baere E (2015) Novel FRMD7 mutations and genomic rearrangement expand the molecular pathogenesis of X-linked idiopathic infantile nystagmus. Invest Ophthalmol Vis Sci 56(3):1701–1710CrossRefGoogle Scholar
- Chishti AH, Kim AC, Marfatia SM, Lutchman M, Hanspal M, Jindal H, Liu SC, Low PS, Rouleau GA, Mohandas N, Chasis JA, Conboy JG, Gascard P, Takakuwa Y, Huang SC, Benz EJ Jr, Bretscher A, Fehon RG, Gusella JF, Ramesh V, Solomon F, Marchesi VT, Tsukita S, Tsukita S, Arpin M, Louvard D, Tonks NK, Anderson JM, Fanning AS, Bryant PJ, Woods DF, Hoover KB (1998) The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends Biochem Sci 23(8):281–282Google Scholar
- Self J, Lotery A (2007) A review of the molecular genetics of congenital idiopathic nystagmus (CIN). Ophthalmic Genet 28(4):187–191Google Scholar
- Tarpey P, Thomas S, Sarvananthan N, Mallya U, Lisgo S, Talbot CJ, Roberts EO, Awan M, Surendran M, McLean RJ, Reinecke RD, Langmann A, Lindner S, Koch M, Jain S, Woodruff G, Gale RP, Bastawrous A, Degg C, Droutsas K, Asproudis I, Zubcov AA, Pieh C, Veal CD, Machado RD, Backhouse OC, Baumber L, Constantinescu CS, Brodsky MC, Hunter DG, Hertle RW, Read RJ, Edkins S, O'Meara S, Parker A, Stevens C, Teague J, Wooster R, Futreal PA, Trembath RC, Stratton MR, Raymond FL, Gottlob I (2006) Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus. Nat Genet 38(11):1242–1244CrossRefGoogle Scholar
- Thomas MG, Crosier M, Lindsay S, Kumar A, Thomas S, Araki M, Talbot CJ, McLean RJ, Surendran M, Taylor K, Leroy BP, Moore AT, Hunter DG, Hertle RW, Tarpey P, Langmann A, Lindner S, Brandner M, Gottlob I (2011) The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus. Brain 134(Pt 3):892–902CrossRefGoogle Scholar
- Watkins RJ, Thomas MG, Talbot CJ, Gottlob I, Shackleton S (2012) The role of FRMD7 in idiopathic infantile nystagmus. J Ophthalmol 2012:460956Google Scholar
- Zhang X, Ge X, Yu Y, Zhang Y, Wu Y, Luan Y, Sun J, Qu J, Jin ZB, Gu F (2014) Identification of three novel mutations in the FRMD7 gene for X-linked idiopathic congenital nystagmus. Sci Rep 4:3745Google Scholar
- Zhao H, Huang XF, Zheng ZL, Deng WL, Lei XL, Xing DJ, Ye L, Xu SZ, Chen J, Zhang F, Yu XP, Jin ZB (2016) Molecular genetic analysis of patients with sporadic and X-linked infantile nystagmus. BMJ Open 6(4):e010649Google Scholar