Williamson Kathleen A, FitzPatrick David R
Medical Research Council Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Medical Research Council Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Eur J Med Genet. 2014 Aug;57(8):369-80. doi: 10.1016/j.ejmg.2014.05.002. Epub 2014 May 22.
Microphthalmia, anophthalmia and coloboma (MAC) are distinct phenotypes that represent a continuum of structural developmental eye defects. In severe bilateral cases (anophthalmia or severe microphthalmia) the genetic cause is now identifiable in approximately 80 percent of cases, with de novo heterozygous loss-of-function mutations in SOX2 or OTX2 being the most common. The genetic cause of other forms of MAC, in particular isolated coloboma, remains unknown in the majority of cases. This review will focus on MAC phenotypes that are associated with mutation of the genes SOX2, OTX2, PAX6, STRA6, ALDH1A3, RARB, VSX2, RAX, FOXE3, BMP4, BMP7, GDF3, GDF6, ABCB6, ATOH7, C12orf57, TENM3 (ODZ3), and VAX1. Recently reported mutation of the SALL2 and YAP1 genes are discussed in brief. Clinical and genetic features were reviewed in a total of 283 unrelated MAC cases or families that were mutation-positive from these 20 genes. Both the relative frequency of mutations in MAC cohort screens and the level of confidence in the assignment of disease-causing status were evaluated for each gene.
小眼症、无眼症和脉络膜缺损（MAC）是不同的表型，代表了一系列结构性发育性眼部缺陷。在严重的双侧病例（无眼症或严重小眼症）中，目前约80%的病例可确定遗传病因，其中SOX2或OTX2的新生杂合功能丧失突变最为常见。在大多数情况下，其他形式的MAC，特别是孤立性脉络膜缺损的遗传病因仍不清楚。本综述将聚焦于与SOX2、OTX2、PAX6、STRA6、ALDH1A3、RARB、VSX2、RAX、FOXE3、BMP4、BMP7、GDF3、GDF6、ABCB6、ATOH7、C12orf57、TENM3（ODZ3）和VAX1基因突变相关的MAC表型。最近报道的SALL2和YAP1基因的突变将作简要讨论。对这20个基因中283例突变阳性的无关MAC病例或家系的临床和遗传特征进行了综述。对每个基因评估了MAC队列筛查中突变的相对频率以及致病状态判定的置信水平。
