Correlations of FRMD7 gene mutations with ocular oscillations

Abstract

Mutations in the FERM domain containing 7 (FRMD7) gene have been proven to be responsible for infantile nystagmus (IN). The purpose of this study is to investigate FRMD7 gene mutations in patients with IN, and to evaluate the nystagmus intensity among patients with and without FRMD7 mutations. The affected males were subdivided into three groups according to whether or not having FRMD7 mutations and the types of mutations. Fifty-two mutations were detected in FRMD7 in 56 pedigrees and 34 sporadic patients with IN, including 28 novel and 24 previous reported mutations. The novel identified mutations further expand the spectrum of FRMD7 mutations. The parameters of nystagmus intensity and the patients' best corrected visual acuity were not statistically different among the patients with and without identified FRMD7 mutations, and also not different among patients with different mutant types. The FERM-C domain, whose amino acids are encoded by exons 7, 8 and 9, could be the harbor region for most mutations. Loss-of-function is suggested to be the common molecular mechanism for the X-linked infantile nystagmus.

Figure 1

Schematic representation of 28 novel FRMD7 mutations.

Figure 2

Distribution of 52 Mutations in the FRMD7 gene.

Figure 3

FRMD7 mutation and waveforms recorded in two families. The probands in families A and B (denoted by the black arrows) carried the same mutation of c.773 T > C (p.M258T) in exon 9 (C). Nystagmus was recorded as horizontal pendular waveforms from the proband (D, middle panel), and as decelerating exponential slow phase jerk waveforms from his mother (D, upper panel) in the Family A. As a control, his father had normal eye movement recordings (D, lower panel). The proband in Family B showed horizontal decelerating exponential slow phase jerk waveforms (E, middle panel), and his mother had horizontal dual jerk waveforms (E, upper panel), compared with his father (E, lower panel). A 3-D model construction showed a wild-type nonpolar amino acid of Methionine (F) was replaced by a charged and polar amino acid of Threonine (G), which would damage the stability of the protein structure and function.

Figure 4

Box plots showing median levels of the BCVA in three groups of patients.

Figure 5

Box plots showing median levels of the amplitude in three groups of patients.

Figure 6

Box plots showing median levels of the frequency in three groups of patients.

Figure 7

Distribution of FRMD7 mutations within exons identified in this study and previous reports.

Figure 8

Proportions of FRMD7 mutation types identified in this study and reported recently.