Comprehensive analysis of pathogenic genes and clinical phenotypes in patients with Leber congenital amuarosis
10.3760/cma.j.cn511434-20211116-00643
- VernacularTitle:Leber先天性黑矇患者致病基因与临床表型分析
- Author:
Dongjun XING
1
;
Zhiqing LI
;
Rongguo YU
;
Linni WANG
;
Liying HU
;
Yang YANG
;
Chang LI
;
Xiaorong LI
Author Information
1. 天津医科大学眼科医院、眼视光学院、眼科研究所 国家眼耳鼻喉疾病临床医学研究中心天津市分中心 天津市视网膜功能与疾病重点实验室, 天津 300384
- Keywords:
Leber congenital amaurosis;
Genes;
Mutation;
GUCY2D gene;
CRB1 gene
- From:
Chinese Journal of Ocular Fundus Diseases
2022;38(8):663-667
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe clinical phenotypes and analyze the pathogenic genes of Leber congenital amaurosis (LCA).Methods:A retrospective clinical study. From 2019 to 2020, 2 patients diagnosed with LCA by genetic testing in Tianjin Medical University Eye Hospital and their 6 unaffected family members were enrolled in the study. Two patients were from 2 unrelated families, both were probands. The patient's medical history was inquired in detail, slit lamp microscopy, ultra-widefield fundus photography, autofluorescence, and flash visual evoked potential (F-VEP) were performed. Peripheral vein blood (3-5 ml) was collected and genomic DNA was extracted from all study subjects. A total of 381 pathogetic genes associated with inherited retinal diseases, were selected by targeted exome sequencing capture strategy. Sanger sequencing was used to verify suspected pathogenic mutations. Candidate pathogenic mutations were identified after bioinformatics analysis. Sanger sequencing, real-time quantitative polymerase chain reaction and family co-identification were used to confirm the final mutations.Results:Two patients were male, aged 3 and 27 years. One case had vision loss in both eyes, accompanied by nystagmus and acupressure eye sign since childhood. The clinical hallmark of the proband (F1-Ⅱ-3) in F1 includes clearly boundary of optic disc, normal retinal blood vessels and macular fovea. The implied period of the maximum forward wave in both eyes of F-VEP was roughly normal, and its amplitude decreased significantly. The phenotype of the proband (F2-Ⅱ-1) in F2 includes optic nerve head pallor, bone-spicule intraretinal pigmentation, "gold-foil maculopathy" , retina patchy hypo-autofluorescence in both eyes. There was no abnormal phenotype in the eyes of the family members. According to the genetic diagnosis, the proband (F1-Ⅱ-3) carried the GUCY2D gene c.835G>A (p.D279N) (M1) and exon 9-19 deletion (M2) compound heterozygous mutations, in which M1 was derived from healthy mother and M2 was derived from healthy father. The proband (F2-Ⅱ-1) carried CRB1 gene c.1576C>T(R526X) (M3) and c.1522T>C (C508R) (M4) compound heterozygous mutations, in which M3 from the healthy father, M4 from the healthy mother. M2 and M4 were novel mutations. Conclusion:GUCY2D gene mutations lead to LCA1 type in the F1 family, CRB1 gene mutations lead to LCA8 type in the F2 family; there are significant different phenotypes caused by different pathogenic genes.
