X-linked Opitz syndrome:: Gene and redefinition of the novel mutations in the MID1 clinical spectrum
X-linked Opitz syndrome:: Gene and redefinition of the novel mutations in the MID1 clinical spectrum
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DOI：
10.1002/ajmg.a.10265
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发表时间：
2003-07-15
影响因子：
2
通讯作者：
Meroni, G
中科院分区：
文献类型：
--
作者：
De Falco, F;Cainarca, S;Meroni, G
Opitz（或 G/BBB）综合征是一种多效性遗传性疾病，其特征是距离过远、尿道下裂和其他中线缺陷。该综合征具有异质性，有 X 连锁 (XLOS) 和常染色体显性 (ADOS) 形式。 XLOS 形式中涉及的基因 MIDI 编码含有属于三联基序 (TRIM) 家族的 RING-Bbox-Coiled-coil 基序的蛋白质。为了进一步阐明 XLOS 的分子基础，我们对 Opitz 综合征 (OS) 患者的 MIDI 基因进行了突变分析。我们在 63 名男性个体中发现了 11 名新突变，这些男性被称为散发性或家族性 X 连锁 OS 病例。这些突变分散在整个基因中，但更多的突变出现在 3' 区域。通过回顾迄今为止描述的所有 MID1 突变 OS 患者，我们证实距离过远和尿道下裂是最常见的表现，几乎存在于每个 XLOS 个体中。然而，很明显，喉-气管-食管 (LTE) 缺陷也是常见的异常，所有 MID1 突变的男性患者都会出现这种情况。先天性心脏和肛门异常的发生率低于文献报道的频率。此外，我们可以在 OS 临床概要中包括肢体缺陷，因为我们发现一名 MID1 突变患者表现出并趾。 MID1 突变频率较低且表型变异性较高，表明其他基因也参与了 OS 表型。 (C) 2003 Wiley-Liss, Inc.
Opitz (or G/BBB) syndrome is a pleiotropic genetic disorder characterized by hypertelorism, hypospadias, and additional midline defects. This syndrome is heterogeneous with an X-linked (XLOS) and an autosomal dominant (ADOS) form. The gene implicated in the XLOS form, MIDI, encodes a protein containing a RING-Bbox-Coiled-coil motif belonging to the tripartite motif (TRIM) family. To further clarify the molecular basis of XLOS, we have undertaken mutation analysis of the MIDI gene in patients with Opitz syndrome (OS). We found novel mutations in 11 of 63 male individuals referred to us as sporadic or familial X-linked OS cases. The mutations are scattered throughout the gene, although more are represented in the 3' region. By reviewing all the MID1-mutated OS patients so far described, we confirmed that hypertelorism and hypospadias are the most frequent manifestations, being present in almost every XLOS individual. However, it is clear that laryngo-tracheo-esophageal (LTE) defects are also common anomalies, being manifested by all MID1-mutated male patients. Congenital heart and anal abnormalities are less frequent than reported in literature. In addition, we can include limb defects in the OS clinical synopsis as we found a MID1-mutated patient showing syndactyly. The low frequency of mutations in MID1 and the high variability of the phenotype suggest the involvement of other genes in the OS phenotype. (C) 2003 Wiley-Liss, Inc.