Ophthalmic phenotype of TCIRG1 gene mutations in Chinese infantile malignant osteopetrosis

OBJECTIVE: To evaluate the ophthalmic phenotypes associated with T-cell immune regulator 1 (TCIRG1) mutations in Chinese patients with infantile malignant osteopetrosis (IMO). METHODS AND ANALYSIS: 27 Chinese TCIRG1-related osteoporosis infants were enrolled using direct DNA sequencing of PCR-amplified exons. 12 cases had frameshift mutation (the frameshift mutation group, group F), and 15 cases had point mutation (the point mutation group, group P). The clinical features of the two groups were compared, including age at onset, gaze qualities, optic atrophy, optic canal stenosis and waveforms of Flash visual-evoked potential (FVEP). RESULTS: The clinical signs, except age at onset and FVEP, showed statistically significant differences between the two groups. The mean age at onset was 1.8 months in group F and 4.3 months in group P; 22 eyes (92%) with frameshift mutation and 16 (53%) with point mutation had poor gaze qualities, such as nystagmus and/or strabismus; optic atrophy was found in 16 eyes (67%) in group F and 6 (20%) in group P; the average optic canal diameter was 1.45 mm in the frameshift mutation cases, 1.87 mm in other cases; FVEP indicated that the waveforms in 10 eyes (42%) were not elicited in group F, yet five eyes (17%) in group P. CONCLUSION: In Chinese TCIRG1-related patients of IMO, the optic canal stenosis and optic atrophy were more serious in cases with frameshift mutations. However, no differences in the conduction block of optic nerve were found between the two groups.