Vincent Marie-Claire, Gallai Raffaella, Olivier David, Speeg-Schatz Claude, Flament Jacques, Calvas Patrick, Dollfus Hélène
Service de Génétique Médicale, CHU de Toulouse-Hôpital Purpan, Toulouse, France.
Am J Ophthalmol. 2004 Dec;138(6):1016-21. doi: 10.1016/j.ajo.2004.08.003.
Several ocular defects have been identified as a consequence of the PAX6 gene mutations. With regard to the implication of this gene in unusual phenotypes, we report a family presenting with congenital nystagmus, foveal hypoplasia, and iris hypoplasia or atypical coloboma.
Observational case report.
The entire transcribed region of the PAX6 gene was submitted to mutation search at the DNA and mRNA levels in five affected members of a French family in test with 82 normal subjects.
A novel heterozygous PAX6 gene splice mutation (IVS4 + 5G>C) was identified. The mutation is located in IVS4 within the consensus donor splice site. A mutant mRNA lacking exon 4 as the sole defect was evidenced. The resultant protein was predicted to contain a cryptic ATG initiation codon in exon 3 and a slightly altered paired-domain in an open reading frame extended by 13 amino acids.
The association of anterior segment anomalies and foveal hypoplasia with one of the slightest alterations of the PAX6 protein described to date confirms the association of variant phenotypes with hypomorphic alleles. Mutation screening of the PAX6 gene could be useful in elucidating the origin of complex ocular malformations.
已发现多种眼部缺陷是PAX6基因突变的结果。关于该基因在异常表型中的作用，我们报告了一个患有先天性眼球震颤、黄斑发育不全以及虹膜发育不全或非典型缺损的家系。
观察性病例报告。
在一个法国家系的5名患病成员中，对PAX6基因的整个转录区域进行DNA和mRNA水平的突变筛查，并与82名正常受试者进行对照。
鉴定出一种新的杂合PAX6基因剪接突变（IVS4 + 5G>C）。该突变位于共有供体剪接位点内的IVS4中。证实了突变的mRNA缺少外显子4作为唯一缺陷。预测所得蛋白质在外显子3中含有一个隐蔽的ATG起始密码子，并且在一个延长了13个氨基酸的开放阅读框中，配对结构域略有改变。
前段异常和黄斑发育不全与迄今为止所描述的PAX6蛋白最轻微改变之一相关联，这证实了变异表型与亚效等位基因的关联。PAX6基因的突变筛查可能有助于阐明复杂眼部畸形的起源。
