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Abstract：
Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is due to heterozygous FOXL2 intragenic mutations in about 70% of the patients, whereas total or partial gene deletions account for a minority of cases. Alteration of FOXL2 regulatory elements has been rarely described in patients with BPES. In this study, a prepubertal girl with BPES due to a 197-kb de novo deletion of the regulatory elements upstream of FOXL2 is reported. This girl presented with additional clinical features such as a soft cleft palate and microcephaly; thus, this copy number variant might have other somatic effects. The present deletion encompasses 2 coding genes (MRPS22 and COPB2), whose homozygous mutations have been associated with microcephaly. In our case, the sequences of the non-deleted allele were normal, ruling out a compound genetic defect. Normal levels of new biomarkers of ovarian reserve (anti-müllerian hormone, inhibin B) likely indicate an early diagnosis of type 2 BPES, but an evolutive gonadal damage will be excluded only by long-term follow-up. Additional reports of microdeletions upstream of FOXL2 are needed to better define the underlying genetic mechanism and the related phenotypic spectrum; the ability of the new hormonal markers to predict ovarian function in adolescence and adulthood should be confirmed.
摘要：
咽炎，上睑下垂,和内chan倒肌综合征（BPES）是由于大约70％的患者中的杂合FOXL2基因内突变，而全部或部分基因缺失占少数病例。在BPES患者中很少描述FOXL2调节元件的改变。在这项研究中,据报道，由于FOXL2上游的调节元件从头缺失197kb，因此患有BPES的青春期前女孩。该女孩表现出其他临床特征，例如软left裂和小头畸形；因此，这种拷贝数变异可能有其他体细胞效应.本缺失包括2个编码基因（MRPS22和COPB2），其纯合突变与小头畸形有关。在我们的案例中,非缺失等位基因序列正常,排除复合基因缺陷.卵巢储备新生物标志物的正常水平（抗苗勒管激素，抑制素B）可能表明2型BPES的早期诊断，但是只有通过长期随访才能排除进化性腺损伤.需要进一步报道FOXL2上游的微缺失，以更好地定义潜在的遗传机制和相关的表型谱；应该确认新的激素标记物预测青春期和成年期卵巢功能的能力。
