Genotype-Phenotype Analysis and Mutation Spectrum in a Cohort of Chinese Patients With Congenital Nystagmus.

Congenital nystagmus (CN) is a genetically and clinically heterogeneous ocular disorder that manifests as involuntary, periodic oscillations of the eyes. To date, only and have been reported to be responsible for causing CN. Here, we aimed to identify the disease-causing mutations and describe the clinical features in the affected members in our study. All the subjects underwent a detailed ophthalmic examination. Direct sequencing of all coding exons and splice site regions in and and a mutation assessment were performed in each patient. We found 14 mutations in 14/37 (37.8%) probands, including nine mutations in the gene and five mutations in the gene, seven of which are novel, including c.284G>A(R95K), c.964C>T(P322S), c.284+10T>G, c.901T>C (Y301H), and c.2014_2023delTCACCCATGG(S672Pfs12) in , and c.250+1G>C, and c.485G>A (W162) in . The mutation detection rate was 87.5% (7/8) of familial vs. 24.1% (7/29) of sporadic cases. Ten mutations in 24 (41.7%) non-syndromic subjects and 4 mutations in 13(30.8%) syndromic subjects were detected. A total of 77.8% (7/9) of mutations in were concentrated within the FERM and FA domains, while all mutations in were located in exons 1, 2, 4 and 6. We observed that visual acuity tended to be worse in the group than in the group, and no obvious difference in other clinical manifestations was found through comparisons in different groups of patients. This study identified 14 mutations (seven novel and seven known) in eight familial and 29 sporadic patients with congenital nystagmus, expanding the mutational spectrum and validating and as mutation hotspots. These findings also revealed a significant difference in the screening rate between different groups of participants, providing new insights for the strategy of genetic screening and early clinical diagnosis of CN.