Abouzeid Hana, Youssef Mohamed A, ElShakankiri Nihal, Hauser Philippe, Munier Francis L, Schorderet Daniel F
Jules-Gonin Eye Hospital, University of Lausanne, Switzerland.
Mol Vis. 2009 Oct 17;15:2074-83.
To report the clinical and genetic study of patients with autosomal dominant aniridia.
We studied ten patients with aniridia from three families of Egyptian origin. All patients underwent full ophthalmologic, general and neurological examination, and blood drawing. Cerebral magnetic resonance imaging was performed in the index case of each family. Genomic DNA was prepared from venous leukocytes, and direct sequencing of all the exons and intron-exon junctions of the Paired Box gene 6 (PAX6) was performed after PCR amplification. Phenotype description, including ophthalmic and cerebral anomalies, mutation detection in PAX6 and phenotype-genotype correlation was acquired.
Common features observed in the three families included absence of iris tissue, corneal pannus with different degrees of severity, and foveal hypoplasia with severely reduced visual acuity. In Families 2 and 3, additional findings, such as lens dislocation, lens opacities or polar cataract, and glaucoma, were observed. We identified two novel (c.170-174delTGGGC [p.L57fs17] and c.475delC [p.R159fs47]) and one known (c.718C>T [p.R240X]) PAX6 mutations in the affected members of the three families. Systemic and neurological examination was normal in all ten affected patients. Cerebral magnetic resonance imaging showed absence of the pineal gland in all three index patients. Severe hypoplasia of the brain anterior commissure was associated with the p.L57fs17 mutation, absence of the posterior commissure with p.R159fs47, and optic chiasma atrophy and almost complete agenesis of the corpus callosum with p.R240X.
We identified two novel PAX6 mutations in families with severe aniridia. In addition to common phenotype of aniridia and despite normal neurological examination, absence of the pineal gland and interhemispheric brain anomalies were observed in all three index patients. The heterogeneity of PAX6 mutations and brain anomalies are highlighted. This report emphasizes the association between aniridia and brain anomalies with or without functional impact, such as neurodevelopment delay or auditory dysfunction.
报告常染色体显性无虹膜患者的临床及遗传学研究。
我们研究了来自三个埃及裔家族的10例无虹膜患者。所有患者均接受了全面的眼科、全身及神经学检查，并进行了采血。对每个家族的先证者进行了脑部磁共振成像检查。从静脉白细胞中提取基因组DNA，经聚合酶链反应（PCR）扩增后，对配对盒基因6（PAX6）的所有外显子及内含子-外显子连接区进行直接测序。获取了包括眼科及脑部异常的表型描述、PAX6突变检测及表型-基因型相关性。
在这三个家族中观察到的共同特征包括虹膜组织缺失、不同严重程度的角膜血管翳以及黄斑发育不全伴视力严重下降。在家族2和家族3中，还观察到其他表现，如晶状体脱位、晶状体混浊或极性白内障以及青光眼。我们在这三个家族的患病成员中鉴定出两个新的（c.170 - 174delTGGGC [p.L57fs17]和c.475delC [p.R159fs47]）以及一个已知的（c.718C>T [p.R240X]）PAX6突变。所有10例患病患者的全身及神经学检查均正常。脑部磁共振成像显示，所有三位先证者均无松果体。严重的脑前连合发育不全与p.L57fs17突变相关，后连合缺失与p.R159fs47相关，视交叉萎缩及胼胝体几乎完全缺如与p.R240X相关。
我们在严重无虹膜家族中鉴定出两个新的PAX6突变。除了无虹膜的常见表型外，尽管神经学检查正常，但在所有三位先证者中均观察到松果体缺失及脑半球间异常。突出了PAX6突变及脑异常的异质性。本报告强调了无虹膜与脑异常之间的关联，无论有无功能影响，如神经发育延迟或听觉功能障碍。
