Abouzeid Hana, Meire Françoise M, Osman Ihab, ElShakankiri Nihal, Bolay Sylvain, Munier Francis L, Schorderet Daniel F
Jules-Gonin Eye Hospital, University of Lausanne, Switzerland.
Ophthalmology. 2009 Jan;116(1):154-162.e1. doi: 10.1016/j.ophtha.2008.08.044. Epub 2008 Nov 12.
To report a novel phenotype of autosomal dominant atypical congenital cataract associated with variable expression of microcornea, microphthalmia, and iris coloboma linked to chromosome 2. Molecular analysis of this phenotype may improve our understanding of anterior segment development.
Observational case study, genome linkage analysis, and gene mutation screening.
Three families, 1 Egyptian and 2 Belgians, with a total of 31 affected were studied.
Twenty-one affected subjects and 9 first-degree relatives underwent complete ophthalmic examination. In the Egyptian family, exclusion of PAX6, CRYAA, and MAF genes was demonstrated by haplotype analysis using microsatellite markers on chromosomes 11, 16, and 21. Genome-wide linkage analysis was then performed using 385 microsatellite markers on this family. In the 2 Belgian families, the PAX6 gene was screened for mutations by direct sequencing of all exons.
Phenotype description, genome-wide linkage of the phenotype, linkage to the PAX6, CRYAA, and MAF genes, and mutation detection in the PAX6 gene.
Affected members of the 3 families had bilateral congenital cataracts inherited in an autosomal dominant pattern. A novel form of hexagonal nuclear cataract with cortical riders was expressed. Among affected subjects with available data, 95% had microcornea, 39% had microphthalmia, and 38% had iris coloboma. Seventy-five percent of the colobomata were atypical, showing a nasal superior location in 56%. A positive lod score of 4.86 was obtained at theta = 0 for D2S2309 on chromosome 2, a 4.9-Mb common haplotype flanked by D2S2309 and D2S2358 was obtained in the Egyptian family, and linkage to the PAX6, CRYAA, or MAF gene was excluded. In the 2 Belgian families, sequencing of the junctions and all coding exons of PAX6 did not reveal any molecular change.
We describe a novel phenotype that includes the combination of a novel form of congenital hexagonal cataract, with variably expressed microcornea, microphthalmia, and atypical iris coloboma, not caused by PAX6 and mapping to chromosome 2.
FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.
报告一种常染色体显性非典型先天性白内障的新表型，其与小角膜、小眼症和虹膜缺损的可变表达相关，这些症状与2号染色体有关。对该表型进行分子分析可能会增进我们对眼前节发育的理解。
观察性病例研究、全基因组连锁分析和基因突变筛查。
三个家族，1个埃及家族和2个比利时家族，共31名患者接受研究。
21名患者和9名一级亲属接受了全面的眼科检查。在埃及家族中，通过使用11号、16号和21号染色体上的微卫星标记进行单倍型分析，排除了PAX6、CRYAA和MAF基因。然后使用该家族中的385个微卫星标记进行全基因组连锁分析。在2个比利时家族中，通过对PAX6基因的所有外显子进行直接测序来筛查突变。
表型描述、该表型的全基因组连锁分析、与PAX6、CRYAA和MAF基因的连锁分析以及PAX6基因中的突变检测。
这3个家族的患病成员均患有以常染色体显性模式遗传的双侧先天性白内障。表现出一种新型的带有皮质嵴的六角形核性白内障。在有可用数据的患者中，95%有小角膜，39%有小眼症，38%有虹膜缺损。75%的缺损为非典型性，56%位于鼻上方。在2号染色体上的D2S2309位点，θ = 0时获得了4.86的正对数优势分数，在埃及家族中获得了一个位于D2S2309和D2S2358之间的4.9 Mb常见单倍型，并且排除了与PAX6、CRYAA或MAF基因的连锁关系。在2个比利时家族中，PAX6基因连接区和所有编码外显子的测序未发现任何分子变化。
我们描述了一种新表型，其包括一种新型先天性六角形白内障，伴有可变表达的小角膜、小眼症和非典型虹膜缺损，并非由PAX6引起，且定位于2号染色体。
作者对本文中讨论的任何材料均无专利或商业利益。
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