RÉSUMÉ
Objective:To investigate the relationship between genotype and phenotype in children with CRB1 mutated Leber congenital amaurosis (LCA) and early onset retinal dystrophy (EOSRD). Methods:A retrospective clinical study. From January 2013 to December 2019, 10 children with CRB1 mutated LCA/EOSRD were enrolled in the study. The patients were identified as CRB1 mutation by the second generation targeted capture sequencing, Sanger sequencing and the family segregation analysis. All children underwent electroretinogram (ERG) and fundus examination. At the same time, 6 cases were examined by optical coherence tomography (OCT); 1 case was examined by fluorescein fundus angiography (FFA), 7 cases were examined by wide-angle laser scanning ophthalmoscope (UWF SLO). Results:There were 6 cases of LCA and 4 cases of EOSRD in 10 patients with CRB1 gene mutations. The average age of first visit was 3.61 years old. The light and dark wave of ERG was flat in 6 cases, and decreased in 4 cases. A total of 19 pathogenic mutations were detected. There were 1 homozygous mutation and 9 compound heterozygous mutations. There were 4, 2 and 1 cases of "copper-coin" like, "salt and pepper" like and "osteocyte" like pigment changes in retina, 1 case of "crystalline pigment" change and 2 cases of macular pigment scar. In 7 cases of UWF SLO examination, different degrees of para-arteriolar pigment epithelium retention (PPRPE) were found in the middle and peripheral fundus. In 6 cases examined by OCT, the outer layer of retina atrophied and the band of ellipsoid disappeared. Symmetrical cystoid macular edema, splitting cystoid macular degeneration and adhesion of epi-macular membrane to optic disc and macular area were found in 1 case, respectively, the retinal structure was rough and thickened, and the fovea became thinner in 3 cases. In FFA examination, 1 case showed uveitis-like changes with late optic disc fluorescein staining, macular fluorescence accumulation, strong fluorescence diffusing along the blood vessels in each quadrant, peripheral PPRPE of "frost-branch" like strong fluorescence. Conclusion:The relationship between genotype and phenotype of CRB1 mutation is complex, and PPRPE is a common characteristic change.
RÉSUMÉ
Granular corneal dystrophy is a rare autosomal dominant genetic disease in clinic.Due to the TGFBI mutation on the 5q31 chromosome,the TGFBIp abnormally aggregates in the Bowman layer and the matrix layer and metabolic disorders,patients' bilateral cornea arise opacity,making visual acuity Progressive impairment.At present,there are at least 66 TGFBI mutations,at least 10 of which are related to granular corneal dystrophy,due to variation in genotype and the difference between homozygous and heterozygous,the patients' phenotype shows a significant difference.Along with the improvement of people's cognition,and the application of laser scanning confocal microscope and the gene diagnosis,More and more patients get the correct diagnosis,Current treatment methods mainly include corneal transplantation and laser ablation,patients are not satisfied because of the postoperative recurrence and aggravated.Due to the establishment of granular corneal dystrophy animal model,lithium and gene therapy will show a good application prospects.