Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus

Abstract

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.

Figure 1. Refinement of the linkage interval to Xq26 and the pattern of expression of FRMD7 in brain of human embryos ∼56 dpo by in situ hybridization

(a) shows the pedigree N1 with the critical individuals marked with an arrow whose haplotype define the minimum critical linkage interval (b) the allele size for marker DXS1047 is discordant in individual IV9 with the other affected males, V2 and VI2 and the allele size at markers DXS1041 and DXS8050 in individual VI2 is discordant as compared to individuals V2 and IV9 (c) the location of LOC90167 is shown relative to the linkage markers DXS8072 and DXS807 (d) A 599 bp and a 681 bp probe from unique sequence in the 3′UTR of FRMD7 were used as probes for in situ hybridization. Panels a and c show in situ hybridization results using sense probes, b and d use antisense probes in similar anatomical locations. Panels a and b are sagittal sections showing the lateral ventricle(v), cerebellar peduncle (cp) and developing neural retina(r). Panel e is an enlargement of panel b to illustrate the retina. Panels c and d are transverse sections showing the spinal cord (s), hypothalamus (h) and cerebellar peduncle. In panel b the scale bar = 2000μm and in panel d =1800μm.