AIM:To conduct a screening of disease-causing genes mutations for a sick family of congenital nuclear cataract in order to explore its potential genetic defects. METHODS:After a detailed history taking and clinical examination, mutation detection of the candidate genes for nuclear cataract was conducted with the application of PCR-direct sequencing on the proband and the other 9 patients of his family,11 blood-related normal family members and 20 unrelated normal controls . RESULTS:c.139G> A heterozygous missense mutation was found in GJA8 gene of this family patients, leading to the change of No.47 highly conserved aspartic acid into asparagine (p.D47N), but the normal family members and normal controls were not found in the mutant. CONCLUSION: p.D47N mutations in Chinese families of congenital cataract is the first report. The prevalence of this mutation is a potential genetic causes of this sick family, GJA8 gene is one of the congenital cataract disease-causing genes. This study also confirms that congenital cataract is a clinically and genetically heterogeneous disease, such a heterogeneity is more apparent especially between different ethnic groups.