PDF(Pubmed)
Abstract：
BACKGROUND: According to previous reports, PAX6-associated foveal hypoplasia (FH) could usually be accompanied by various anterior segment anomalies including variable iris changes. This study aims to exhibit unusual phenotypes of a novel missense variant of PAX6 from a Chinese pedigree.
METHODS: Ophthalmic examinations including slit-lamp biomicroscopy, gonioscopy, ophthalmic ultrasound, ultrasonic biomicroscopy, optical coherence tomography, wide-field fundus imaging, and visual field test were performed to evaluate the clinical manifestations. Whole-exome sequencing (WES) and bioinformatics analysis were conducted in eight members from this pedigree to identify the causative mutation.
RESULTS: WES revealed a novel heterozygous substitution of PAX6 (NM_000280.5:c.157G > A, p.(Val53Met) (chr11:31823309 C > T, hg19)), which cosegregated with the phenotype of this pedigree. All the three patients (a pair of fraternal twins and their mother) exhibited bilateral FH and anterior segment dysgenesis (ASD) including microcornea, sclerocornea, obvious symmetrical corectopia, iris stromal dysplasia, goniodysgenesis, and abnormal distribution of fundus blood vessels. The girl of the fraternal twins also demonstrated bilateral temporal deviation of lenses and abnormal tissue membrane connecting anterior chamber angle and lens anterior capsule in the right eye. The mother additionally showed apparent cataract bilaterally and cupping of the optic disc in her left eye.
CONCLUSIONS: A novel missense variant in PAX6 gene was detected in a Chinese pedigree demonstrating bilateral FH and ASD. It is really distinctive that the ASD involves almost all parts of the anterior segment, and bilateral symmetrical corectopia is the most perceptible sign. This study expands the phenotypic and genotypic spectrum of PAX6-associated ocular diseases, and facilitates the understanding of the crucial role that PAX6 plays in the development of the eye. Meanwhile, PAX6 could be considered as a candidate pathogenic gene of bilateral symmetrical corectopia.
METHODS: Ophthalmic examinations including slit-lamp biomicroscopy, gonioscopy, ophthalmic ultrasound, ultrasonic biomicroscopy, optical coherence tomography, wide-field fundus imaging, and visual field test were performed to evaluate the clinical manifestations. Whole-exome sequencing (WES) and bioinformatics analysis were conducted in eight members from this pedigree to identify the causative mutation.
RESULTS: WES revealed a novel heterozygous substitution of PAX6 (NM_000280.5:c.157G > A, p.(Val53Met) (chr11:31823309 C > T, hg19)), which cosegregated with the phenotype of this pedigree. All the three patients (a pair of fraternal twins and their mother) exhibited bilateral FH and anterior segment dysgenesis (ASD) including microcornea, sclerocornea, obvious symmetrical corectopia, iris stromal dysplasia, goniodysgenesis, and abnormal distribution of fundus blood vessels. The girl of the fraternal twins also demonstrated bilateral temporal deviation of lenses and abnormal tissue membrane connecting anterior chamber angle and lens anterior capsule in the right eye. The mother additionally showed apparent cataract bilaterally and cupping of the optic disc in her left eye.
CONCLUSIONS: A novel missense variant in PAX6 gene was detected in a Chinese pedigree demonstrating bilateral FH and ASD. It is really distinctive that the ASD involves almost all parts of the anterior segment, and bilateral symmetrical corectopia is the most perceptible sign. This study expands the phenotypic and genotypic spectrum of PAX6-associated ocular diseases, and facilitates the understanding of the crucial role that PAX6 plays in the development of the eye. Meanwhile, PAX6 could be considered as a candidate pathogenic gene of bilateral symmetrical corectopia.
摘要：
背景：根据以前的报道，PAX6相关的中央凹发育不全（FH）通常可伴有各种眼前节异常，包括可变的虹膜变化。这项研究旨在展示来自中国谱系的PAX6的新型错义变体的异常表型。
方法：眼科检查，包括裂隙灯生物显微镜，房角镜检查,眼科超声,超声生物显微镜,光学相干层析成像，宽视野眼底成像,并进行视野测试以评估临床表现。在该谱系的八个成员中进行了全外显子组测序（WES）和生物信息学分析，以鉴定致病突变。
结果：WES揭示了PAX6的新杂合置换（NM_000280.5：c.157G>A，p.(Val53Met)(chr11:31823309C>T，hg19)),与该谱系的表型分离。所有三名患者（一对异卵双胞胎及其母亲）均表现为双侧FH和包括微角膜在内的眼前节发育不全（ASD），巩膜角膜,明显的对称直视，虹膜基质发育不良,淋病发生，眼底血管分布异常。异卵双胞胎的女孩还表现出晶状体的双侧颞侧偏移以及右眼前房角和晶状体前囊连接的异常组织膜。母亲还表现出明显的双侧白内障，左眼视盘拔罐。
结论：在一个显示双侧FH和ASD的中国家系中检测到PAX6基因的新错义变异。非常独特的是，ASD几乎涉及眼前节的所有部分，双侧对称直托症是最明显的标志。这项研究扩展了PAX6相关眼部疾病的表型和基因型谱，并有助于理解PAX6在眼睛发育中的关键作用。同时,PAX6可以被认为是双侧对称直托症的候选致病基因。
方法：眼科检查，包括裂隙灯生物显微镜，房角镜检查,眼科超声,超声生物显微镜,光学相干层析成像，宽视野眼底成像,并进行视野测试以评估临床表现。在该谱系的八个成员中进行了全外显子组测序（WES）和生物信息学分析，以鉴定致病突变。
结果：WES揭示了PAX6的新杂合置换（NM_000280.5：c.157G>A，p.(Val53Met)(chr11:31823309C>T，hg19)),与该谱系的表型分离。所有三名患者（一对异卵双胞胎及其母亲）均表现为双侧FH和包括微角膜在内的眼前节发育不全（ASD），巩膜角膜,明显的对称直视，虹膜基质发育不良,淋病发生，眼底血管分布异常。异卵双胞胎的女孩还表现出晶状体的双侧颞侧偏移以及右眼前房角和晶状体前囊连接的异常组织膜。母亲还表现出明显的双侧白内障，左眼视盘拔罐。
结论：在一个显示双侧FH和ASD的中国家系中检测到PAX6基因的新错义变异。非常独特的是，ASD几乎涉及眼前节的所有部分，双侧对称直托症是最明显的标志。这项研究扩展了PAX6相关眼部疾病的表型和基因型谱，并有助于理解PAX6在眼睛发育中的关键作用。同时,PAX6可以被认为是双侧对称直托症的候选致病基因。
