Identification of copy number variants associated with BPES-like phenotypes
Identification of copy number variants associated with BPES-like phenotypes
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DOI：
10.1007/s00439-008-0574-9
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发表时间：
2008-12-01
期刊：
影响因子：
5.3
通讯作者：
Ruivenkamp, Claudia A. L.
中科院分区：
文献类型：
--
作者：
Gijsbers, Antoinet C. J.;D'haene, Barbara;Ruivenkamp, Claudia A. L.
眼睑下垂-下垂-内眦赘肉倒置综合征（BPES）是一种特征明显的罕见综合征，包括眼睑畸形伴（I型）或无卵巢早衰（II型）。典型BPES患者有睑下垂、上睑下垂、上眦内翻和远眦下垂四大特征。编码叉头转录因子的FOXL2基因突变是导致这两种类型BPES的主要原因。然而，许多具有BPES样特征的患者，即至少具有BPES的两个主要特征，原因不明。在这里，我们报告了一组27例具有bpes样特征的患者，但在FOXL2基因或侧翼区域没有确定的遗传缺陷。对这些患者进行全基因组高密度阵列分析，以确定可能解释bpes样表型的拷贝数变异（CNVs）。在27例患者中，有9例（33%）检测到以前未被描述为多态性的CNVs。其中4名患者表现出精神运动迟缓作为额外的临床特征。总之，我们证明了bp样表型经常是由CNVs引起的，我们强调了全基因组拷贝数筛选的重要性，以确定这些表型的潜在遗传原因。
Blepharophimosis-Ptosis-Epicanthus inversus syndrome (BPES) is a well-characterized rare syndrome that includes an eyelid malformation associated with (type I) or without premature ovarian failure (type II). Patients with typical BPES have four major characteristics: blepharophimosis, ptosis, epicanthus inversus and telecanthus. Mutations in the FOXL2 gene, encoding a forkhead transcription factor, are responsible for the majority of both types of BPES. However, many patients with BPES-like features, i.e., having at least two major characteristics of BPES, have an unidentified cause. Here, we report on a group of 27 patients with BPES-like features, but without an identified genetic defect in the FOXL2 gene or flanking region. These patients were analyzed with whole-genome high-density arrays in order to identify copy number variants (CNVs) that might explain the BPES-like phenotype. In nine out of 27 patients (33%) CNVs not previously described as polymorphisms were detected. Four of these patients displayed psychomotor retardation as an additional clinical characteristic. In conclusion, we demonstrate that BPES-like phenotypes are frequently caused by CNVs, and we emphasize the importance of whole-genome copy number screening to identify the underlying genetic causes of these phenotypes.