Distribution of gene mutations in sporadic congenital cataract in a Han Chinese population.
This study aimed to investigate the genetic effects underlying non-familial sporadic congenital cataract (SCC).



We collected DNA samples from 74 patients with SCC and 20 patients with traumatic cataract (TC) in an age-matched group and performed genomic sequencing of 61 lens-related genes with target region capture and next-generation sequencing (NGS). The suspected SCC variants were validated with MassARRAY and Sanger sequencing. DNA samples from 103 healthy subjects were used as additional controls in the confirmation examination.



By filtering against common variants in public databases and those associated with TC cases, we identified 23 SCC-specific variants in 17 genes from 19 patients, which were predicted to be functional. These mutations were further confirmed by examination of the 103 healthy controls. Among the mutated genes, CRYBB3 had the highest mutation frequency with mutations detected four times in four patients, followed by EPHA2, NHS, and WDR36, the mutation of which were detected two times in two patients. We observed that the four patients with CRYBB3 mutations had three different cataract phenotypes.



From this study, we concluded the clinical and genetic heterogeneity of SCC. This is the first study to report broad spectrum genotyping for patients with SCC.
Research Center, Eye & ENT Hospital of Fudan University, Shanghai, China; Key Laboratory of myopia,Ministry of Health, Shanghai, China.
Dan
D
Li
Department of Ophthalmology, Shanghai Children's Hospital, Shanghai Jiao Tong University; Shanghai,China.
Siying
S
Wang
Key Laboratory of myopia,Ministry of Health, Shanghai, China; Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China.
Hongfei
H
Ye
Key Laboratory of myopia,Ministry of Health, Shanghai, China; Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China.
Yating
Y
Tang
Key Laboratory of myopia,Ministry of Health, Shanghai, China; Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China.
Xiaodi
X
Qiu
Key Laboratory of myopia,Ministry of Health, Shanghai, China; Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China.
Qi
Q
Fan
Key Laboratory of myopia,Ministry of Health, Shanghai, China; Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China.
Xianfang
X
Rong
Key Laboratory of myopia,Ministry of Health, Shanghai, China; Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China.
Xin
X
Liu
Key Laboratory of myopia,Ministry of Health, Shanghai, China; Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China.
Yuhong
Y
Chen
Key Laboratory of myopia,Ministry of Health, Shanghai, China; Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China.
Jin
J
Yang
Key Laboratory of myopia,Ministry of Health, Shanghai, China; Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, China.
Yi
Y
Lu
D044466:Asian People / Q000235:genetics*; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D003459:Crystallins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D036104:Receptor, EphA2 / Q000235:genetics; D038206:beta-Crystallin B Chain / Q000235:genetics
C103908:CRYBB3 protein, human; D003459:Crystallins; D005136:Eye Proteins; D008565:Membrane Proteins; C488621:NHS protein, human; D009687:Nuclear Proteins; C502341:WDR36 protein, human; D038206:beta-Crystallin B Chain; D036104:Receptor, EphA2