Heterogeneous phenotype in a family with the FERM domain-containing 7 gene R335X mutation

Objective: Infantile nystagmus (IN) is characterized by bilateral involuntary, periodic, and predominantly ocular oscillations. In this article, we describe a mutation screen conducted on a 4-generation family in which 4 patients were affected with X-linked IN (XLIN). Design: Experimental study. Participants: A 4-generation Chinese Han family including 4 symptomatic members with IN and 200 normal male controls. Methods: DNA was extracted from peripheral blood, and the FERM domain-containing 7 gene (FRMD7) was amplified on DNA samples of all the available family members. The mutation screen was conducted by performing direct DNA sequencing. Results: A nonsense mutation (R335X) in the FRMD7 gene was identified in 4 male patients and an asymptomatic female member. Conclusions: Although the R335X mutation in the FRMD7 gene has been previously described, the clinical features, including both disease penetrance and severity, among individuals with FRMD7 mutation in our family vary greatly. One female member with the heterozygous R335X mutation had no clinical manifestation of the disease. This incomplete penetrance suggests that random X-chromosome inactivation may play a role in the pathogenesis of IN, and that loss of functional FRMD7 may account for the development of this disorder. Our findings may be helpful in the genetic counseling of patients with nystagmus.