FOXL2 Mutations and Genomic Rearrangements in BPES
FOXL2 Mutations and Genomic Rearrangements in BPES
复制标题
DOI：
10.1002/humu.20807
复制
发表时间：
2009-02-01
期刊：
影响因子：
3.9
通讯作者：
De Baere, Elfride
中科院分区：
文献类型：
--
作者：
Beysen, Diane;De Paepe, Anne;De Baere, Elfride
FOXL2基因是10个叉头基因之一，其突变可导致人类发育障碍，通常伴有眼部症状。已知FOXL2突变可引起睑袋病综合征（BPES），这是一种常染色体遗传病。显性眼睑畸形与卵巢功能障碍相关（I型）或不相关（II型），导致卵巢早衰（POF）。此外，在孤立性POF患者中也发现了一些突变。在这里，我们回顾了所有目前描述的FOXL2序列变异和BPES和POF的基因组重排。使用联合突变检测方法，可以识别大部分（88%）典型BPES患者的潜在遗传缺陷。在我们的BPES队列中发现的所有遗传缺陷中，基因内突变占81%。它们包括沿单外显子基因分布的错义改变、帧移位和无义突变、帧内缺失和重复。基因组重排包括包含FOXL2的缺失和位于其转录单元之外的缺失，分别占BPES队列中所有遗传缺陷的12%和5%。BPES基因检测的挑战之一是建立基因型-表型相关性，主要是关于卵巢表型。然而，基因检测应在遗传咨询的背景下进行，并应系统地辅以多学科临床随访。参与BPES的医疗保健专业人员面临的另一个挑战是眼睑表型的治疗和POF的预防或治疗。
The FOXL2 gene is one of 10 forkhead genes, the mutations of which lead to human developmental disorders, often with ocular manifestations. Mutations in FOXL2 are known to cause blepharophimosis syndrome (BPES), an autosomal. dominant eyelid malformation associated (type I) or not (type II) with ovarian dysfunction, leading to premature ovarian failure (POF). In addition, a few mutations have been described in patients with isolated POF. Here, we review all currently described FOXL2 sequence variations and genomic rearrangements in BPES and POF. Using a combined mutation detection approach, it is possible to identify the underlying genetic defect in major proportion (88%) of typical BPES patients. Of all genetic defects found in our BPES cohort, intragenic mutations represent 81%. They include missense changes, frame-shift and nonsense mutations, in-frame deletions, and duplications, that are distributed along the single-exon gene. Genomic rearrangements comprising both deletions encompassing FOXL2 and deletions located outside its transcription unit, represent 12% and 5% of all genetic defects in our BPES cohort, respectively. One of the challenges of genetic testing in BPES is the establishment of genotype-phenotype correlations, mainly with respect to the ovarian phenotype. Genetic testing should be performed in the context of genetic counseling, however, and should be systematically complemented by a multidisciplinary clinical follow-up. Another challenge for health care professionals involved in BPES is the treatment of the eyelid phenotype and the prevention or treatment of POF.