Congenital arhinia: Molecular-genetic analysis of five patients
Congenital arhinia: Molecular-genetic analysis of five patients
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DOI：
10.1002/ajmg.a.31613
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发表时间：
2007-03-15
影响因子：
2
通讯作者：
Yoshiura, Koh-ichiro
中科院分区：
文献类型：
--
作者：
Sato, Daisuke;Shimokawa, Osamu;Yoshiura, Koh-ichiro
先天性无鼻症，即完全没有鼻子，是一种非常罕见的异常，原因不明。据我们所知，共报告了36例，但还没有对这种异常进行分子遗传学研究。我们遇到了一个散发的先天性无鼻症与从头染色体易位，t（3;12）（q13.2;p11.2）。这使我们通过基于BAC的FISH分析患者的易位断点，并通过全基因组阵列CGH分析基因组中其他可能的缺失/重复。我们在该患者中发现了一个约19 Mb的缺失，从3q11.2到3q 13 -31，但在另一个断点12p11.2处没有任何基因的破坏。由于3q的缺失片段是包含推定的arhinia基因的强有力的候选区域，我们还在其他四名核型正常的arhinia患者中进行了阵列CGH，以及从位于缺失区域的数百个基因中选择的两个基因COL 8A 1和CPOX的突变分析，因为它们在人类颅面发育的早期阶段表达。然而，在四名患者中，在检查的区域中没有拷贝数畸变或两个基因中没有突变。虽然我们的研究未能确定推测的基因，数据可能成为一个线索，以解开arhinia的潜在机制。(c)2007 Wiley-Liss，Inc.
Congenital arhinia, complete absence of the nose, is an extremely rare anomaly with unknown cause. To our knowledge, a total of 36 cases have been reported, but there has been no molecular-genetic study on this anomaly. We encountered a sporadic case of congenital arhinia associated with a de novo chromosomal translocation, t(3;12)(q13.2;p11.2). This led us to analyze the patient by BAC-based FISH for translocation breakpoints and whole-genome array CGH for other possible deletions/duplications in the genome. We found in this patient an approximately 19 Mb deletion spanning from 3q11.2 to 3q13-31 but no disruption of any gene(s) at the other breakpoint, 12p11.2. As the deleted segment at 3q was a strong candidate region containing the putative arhinia gene, we also performed the array CGH in four other arhinia patients with normal karyotypes, as well as Mutation analysis of two genes, COL8A1 and CPOX, selected among hundreds of genes located to the deleted region, because they are expressed during early stages of human craniofacial development. However, in the four patients, there were no copy number aberrations in the region examined or no mutations in the two genes. Although our study failed to identify the putative arhinia gene, the data may become a clue to unravel the underlying mechanism of arhinia. (c) 2007 Wiley-Liss, Inc.