Five novel mutations of the FRMD7 gene in Chinese families with X-linked infantile nystagmus

Abstract

Purpose: Infantile nystagmus (IN) is an inherited disorder characterized by bilateral ocular oscillatory movements. Recently, mutations in FRMD7 were found to be responsible for X-linked idiopathic infantile nystagmus . We investigated the role of the FRMD7 gene mutations in seven Chinese families with infantile nystagmus.

Methods: Linkage analysis was performed with fluorescently labeled microsatellite markers, DXS1001 and DXS1047. Analysis of FRMD7 gene mutations was performed by direct sequence to the whole coding regions and exon-intron boundaries of FRMD7 gene in all affected members in seven families with IN.

Results: Five novel FRMD7 gene mutations, 70 G>T(p.G24W) in exon 2, c.689-690delAG (p.Ser232del) in exon8, c. 782G>A (p.R260Q) and c. 812G>T (p. C271F) in exon 9, and c. 910C>T (R303X) in exon 10, were identified in five of seven Chinese families with X-linked infantile nystagmus. But we didn't detect the FRMD7 gene mutation in one of seven families, although a positive LOD score of 2.42 (thetamax=0.1) was obtained at DXS1047 . We also found the same mutation, which is c. 782G>A (p.R260Q), occurred in two different families.

Conclusions: This is first report that five kinds of FRMD7 gene mutation types occurred in Chinese families with IN, which further support that FRMD7 gene mutations are the underlying pathogenesis of the molecular mechanism for infantile nystagmus.

Figure 1

Pedigrees of seven families with X-linked congenital nystagmus. Squares indicate males, circles indicate females, slashed symbols indicate deceased, black symbols indicate affected individuals, unfilled symbols indicate unaffected individuals, and unaffected, obligate carriers are represented by a dotted circle.

Figure 2

Sequencing results of affected heterozygous females from families A and D and of affected hemizygous males from families B, E, F, and G . Five types of FRMD7 mutations were identified in six families, which were c. 812G>T (p. C271F) in family A, c.689–690delAG (p.Ser232del) in family B, c.70 G>T(p.G24W) in family D, c. 782G>A (p.R260Q) in both families E and F, and c. 910C>T (R303X) in family G.

Figure 3

Alignment of FRMD7 amino acids. The alignment of amino acids around p.G24, p. R260, and p. C271 of FRMD7 revealed evolutionary conservation of the residue from Canis familiaris, Rattus norvegicus, Mus musculus, and Gallus gallus to Homo sapiens.