Novel Mutations in the FRM7D Causing Congenital Nystagmus

Abstract

Purpose:: To report novel mutations in the FRMD7 causing X-linked congenital nystagmus

Methods:: The 12 exons and intron-exon junctions of the FRMD7 gene were PCR amplified and screened by direct sequencing. The obtained sequences were compared to the reference sequence gi.51477526 and base changes were checked in 120 chromosomes.

Results:: Patients from 8 families and 13 male sporadic cases were investigated. In all families, nystagmus was variable, fully penetrant in males. In the largest family, penetrance of nystagmus was reduced to 90%. The size of the other families did not allow for an accurate estimation of the penetrance. Eight families were investigated and in 6 of them, novel mutations were identified. No mutation was observed in the sporadic cases. The following mutations were obsernved: 4 missense mutations (p.W225G, p.R90L, p.H275P), 1 nonsence (Q20X) and 2 splice mutations (g.15431121A>G, g.15473174G>A). In addition, 2 unreported single nucleotide polymorphisms were identified (g.15431436C>T, g. 15442755T>C).

Conclusions:: Recently, Tarpey et al. (2006) identified the gene responsible for X-linked congenital nystagmus and reported mutations in families and sporadic cases. Our analysis confirmed the implication of FRMD7 in congenital X-linked nystagmus and identified novel mutations. Based on reported data, high molecular heterogeneity is expected which will render the molecular diagnosis more difficult.

Keywords: nystagmus • mutations • gene screening