OBJECTIVETo study the mutation of FRMD7 gene in a Chinese family with congenital idiopathic nystagmus.

METHODSForty-six individuals in the Chinese family with congenital idiopathic nystagmus, including 16 patients, 19 normal siblings and 11 spouses, were investigated under informed consent. Genomic DNA of all 46 members was isolated by standard protocol. The X-linked inherited pattern was ascertained by investigating the history of the family members and the clinical feature of each individual. The genome scan on X chromosome was performed after PCR amplification for microsatellite markers. LOD scores were calculated with Linkage 5.1. Direct DNA sequence analysis was carried out to find the gene mutation responsible for the disease.

RESULTSA maximum LOD score of 8.55 (theta=0) was obtained with polymorphic marker DXS1047. Haplotype construction of the family defined the disease interval between DXS8059 and DXS8033. Direct DNA sequence analysis revealed a heterozygous mutation of G990T in exon 9 of the FRMD7 gene in all patients, which was not present in unaffected family members.

CONCLUSIONCongenital nystagmus is a clinically and genetically heterogeneous ocular movement disease. The mutation of G990T of the FRMD7 gene is the underlying molecular pathogenesis for this family with congenital nystagmus.