Ma Shuying, Lu Yao, Shao Xiao, Liu Qingyan, Yin Xin, Xue Min
Graduate School, Bengbu Medical University; Department of Ophthalmology, Anhui No.2 Provincial People's Hospital, Hefei, China.
Front Med (Lausanne). 2025 Jul 24;12:1624834. doi: 10.3389/fmed.2025.1624834. eCollection 2025.
Congenital cataract refers to lens opacity present at birth or progressively developing in the neonatal period, caused by inherited genetic abnormalities or developmental disorders. The etiology of congenital cataract is multifactorial, and its exact pathogenesis remains incompletely understood. Generally, it can be broadly categorized into genetic factors and non-genetic factors (including environmental influences, intrauterine infections or complications during delivery). This case report presents a hereditary congenital cataract characterized by classical clinical manifestations, high penetrance, and a novel pathogenic gene mutation site that has not been previously documented in medical literature. We herein report this unique case to enhance our understanding of congenital cataract pathogenesis and expand the mutational spectrum associated with this ocular disorder.
A 30-year-old female presented with blurred vision in her left eye since childhood. Slit-lamp microscopy revealed len opacity in the left eye. Based on the patient's age of onset, ocular examination findings, and family history, the diagnosis of congenital cataract was established. Multiple family members had been previously diagnosed with "bilateral congenital cataracts." Following cataract surgery, the patient's visual acuity in the left eye improved to 20/40. To investigate the genetic etiology in this pedigree, whole-exome sequencing was performed on peripheral venous blood samples after obtaining informed consent from the patient and her family. Genetic testing identified a heterozygous missense mutation in exon 2 of the CRYGC gene (c.52G>A:p. Glu18Lys). This mutation results in the substitution of a highly conserved glutamic acid residue with lysine at position 18. Notably, this genetic variant was absent in unaffected family members.
The patients in this pedigree exhibited an autosomal dominant inheritance pattern, with all affected individuals presenting bilateral lens opacities unaccompanied by systemic abnormalities, confirming a definitive diagnosis of congenital cataracts. Genetic screening identified a novel CRYGC gene mutation (c.52G>A:p. Glu18Lys) as the pathogenic cause of congenital cataracts in this family. Our findings expand the mutational spectrum of the CRYGC gene associated with congenital cataracts and provide enhanced insights into the molecular basis of this condition.
先天性白内障是指出生时即存在或在新生儿期逐渐发展的晶状体混浊，由遗传基因异常或发育障碍引起。先天性白内障的病因是多因素的，其确切发病机制仍未完全明确。一般来说，可大致分为遗传因素和非遗传因素（包括环境影响、宫内感染或分娩期间的并发症）。本病例报告介绍了一种遗传性先天性白内障，其具有典型的临床表现、高外显率以及一个医学文献中此前未记载的新的致病基因突变位点。我们在此报告这一独特病例，以增进我们对先天性白内障发病机制的理解，并扩大与这种眼部疾病相关的突变谱。
一名30岁女性自童年起左眼视力模糊。裂隙灯显微镜检查显示左眼晶状体混浊。根据患者的发病年龄、眼部检查结果和家族史，确诊为先天性白内障。此前多名家庭成员被诊断为“双侧先天性白内障”。白内障手术后，患者左眼视力提高到20/40。为了研究该家系的遗传病因，在获得患者及其家人的知情同意后，对外周静脉血样本进行了全外显子组测序。基因检测在CRYGC基因第2外显子中发现一个杂合错义突变（c.52G>A:p.Glu18Lys）。该突变导致第18位高度保守的谷氨酸残基被赖氨酸取代。值得注意的是，未受影响的家庭成员中不存在这种基因变异。
该家系患者表现为常染色体显性遗传模式，所有受影响个体均出现双侧晶状体混浊且无全身异常，确诊为先天性白内障。基因筛查确定了一个新的CRYGC基因突变（c.52G>A:p.Glu18Lys）是该家族先天性白内障的致病原因。我们的研究结果扩大了与先天性白内障相关的CRYGC基因突变谱，并为该病的分子基础提供了更多见解。
