Genetics of anterior segment dysgenesis disorders.
Genetics of anterior segment dysgenesis disorders.
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DOI：
10.1097/icu.0b013e328349412b
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发表时间：
2011-09
影响因子：
3.7
通讯作者：
Semina EV
中科院分区：
文献类型：
--
作者：
Reis LM;Semina EV
眼前节发育不全（ASD）疾病包含一系列影响角膜、虹膜和晶状体的发育状况，通常伴有约50%的青光眼风险。这些疾病的特征是常染色体显性和隐性遗传模式，且往往具有不完全外显率/可变表达性。本文总结了关于ASD疾病遗传学的已知信息，并回顾了近期的研究进展。
在ASD患者中已报道了胶原蛋白4A1（COL4A1）和β -1,3 -葡萄糖基转移酶（B3GALTL）的突变。还介绍了在其他知名眼部基因中的新发现，其中PAX6和PITX2的调控区域缺失最为显著。
尽管已经确定了许多遗传病因，但许多ASD疾病仍有待遗传学上的阐明。大多数已确定特征的ASD基因编码转录因子，一些因子代表细胞外基质相关蛋白。所有相关基因在眼部发育中都发挥积极作用，并在不同物种中表现出保守的功能。使用新技术，如全基因组测序/比较基因组杂交，可能会拓宽已知基因的突变谱，并有助于识别新的致病基因以及解释ASD疾病表型变异的修饰基因。
Anterior segment dysgenesis (ASD) disorders encompass a spectrum of developmental conditions affecting the cornea, iris, and lens and are generally associated with an approximate 50% risk for glaucoma. These conditions are characterized by both autosomal dominant and recessive patterns of inheritance often with incomplete penetrance/variable expressivity. This article summarizes what is known about the genetics of ASD disorders and reviews recent developments. Mutations in Collagen 4A1 (COL4A1) and Beta-1,3-glucosyltransferase (B3GALTL) have been reported in ASD patients. Novel findings in other well-known ocular genes are also presented, among which regulatory region deletions in PAX6 and PITX2 are most notable. Although a number of genetic causes have been identified, many ASD conditions are still awaiting genetic elucidation. The majority of characterized ASD genes encode transcription factors, several factors represent extracellular matrix related proteins. All of the involved genes play active roles in ocular development and demonstrate conserved functions across species. The use of novel technologies, such as whole genome sequencing/comparative genomic hybridization, is likely to broaden the mutation spectrums in known genes and assist in the identification of novel causative genes as well as modifiers explaining the phenotypic variability of ASD conditions.