Deletion at 14q22-23 indicates a contiguous gene syndrome comprising anophthalmia, pituitary hypoplasia, and ear anomalies
Deletion at 14q22-23 indicates a contiguous gene syndrome comprising anophthalmia, pituitary hypoplasia, and ear anomalies
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DOI：
10.1002/ajmg.a.31335
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发表时间：
2006-08-15
影响因子：
2
通讯作者：
Jamieson, Robyn V.
中科院分区：
文献类型：
--
作者：
Nolen, Leisha D.;Amor, David;Jamieson, Robyn V.
无眼症和脑下垂体发育不全都是使人衰弱的疾病，在大多数情况下，潜在的遗传缺陷是未知的。我们发现了一个双侧无眼症和缺乏视神经，视交叉和神经束，以及垂体发育不全和耳畸形的患者与从头明显平衡染色体易位，46，XY，t（3;14）（q28;q23.2）。使用FISH和高分辨率微阵列比较基因组杂交（CGH）的易位断裂点分析已经鉴定了14号染色体长臂上的9.66 Mb缺失区域，其包括基因BMP 4、OTX 27 RTN 1、SIX 6、SIX 1和SIX 4。另外3例涉及14 q22 -23的间质性缺失的患者，均伴有双侧无肛畸形、垂体异常、耳畸形和与我们的患者相似的面部表型。OTX 2参与眼部发育缺陷，并且我们的患者中的眼部表型在其他14 q22 -23缺失患者中的严重性表明该基因组区域含有参与眼部发育的其他基因。基于其表达模式和观察到的鼠突变表型，预测BMP 4单倍不足促成眼部表型。此外，BMP 4和SIX 6的缺失可能与垂体发育异常有关，SIX 1的缺失可能与耳和其他颅面特征有关。这表明14 q22 -23缺失患者的表型特征可能与相邻基因缺失有关。(c)2006 Wiley-Liss，Inc.
Anophthalmia and pituitary gland hypoplasia are both debilitating conditions where the underlying genetic defect is unknown in the majority of cases. We identified a patient with bilateral anophthalmia and absence of the optic nerves, chiasm and tracts, as well as pituitary gland hypoplasia and ear anomalies with a de novo apparently balanced chromosomal translocation, 46,XY,t(3;14)(q28;q23.2). Translocation breakpoint analysis using FISH and high-resolution microarray comparative genomic hybridization (CGH) has identified a 9.66 Mb deleted region on the long arm of chromosome 14 which includes the genes BMP4, OTX27 RTN1, SIX6, SIX1, and SIX4. Three other patients with interstitial deletions involving 14q22-23 have been described, all with bilateral anoplithalmia, pituitary abnormalities, ear anomalies, and a facial phenotype similar to our patient. OTX2 is involved in ocular developmental defects, and the severity of the ocular phenotype in our patient on the other 14q22-23 deletion patients, suggests this genomic region harbors other gene/s involved in ocular development. BMP4 haploinsufficiency is predicted to contribute to the Ocular phenotype on the basis of its expression pattern and observed murine mutant phenotypes. In addition, deletion of BMP4 and SIX6 is likely to contribute to the abnormal pituitary development, and SIX1 deletion may contribute to the ear and other craniofacial features. This indicates that contiguous gene deletion may contribute to the phenotypic features in the 14q22-23 deletion patients. (c) 2006 Wiley-Liss, Inc.