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首页> 外文期刊>Clinical Genetics: An International Journal of Genetics in Medicine >Mutations in PHD-like domain of the ATRX gene correlate with severe psychomotor impairment and severe urogenital abnormalities in patients with ATRX syndrome.
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Mutations in PHD-like domain of the ATRX gene correlate with severe psychomotor impairment and severe urogenital abnormalities in patients with ATRX syndrome.

机译：ATRX基因的PHD样结构域突变与ATRX综合征患者的严重精神运动障碍和严重的泌尿生殖道异常有关。

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摘要

Mutations in ATRX are associated with a wide and clinically heterogeneous spectrum of X-linked mental retardation syndromes. The ATRX protein, involved in chromatin remodelling, belongs to the family of SWI/SNF DNA helicases and contains a plant homeodomain (PHD)-like domain. To date, more than 60 different mutations have been reported in ATRX. One of them is recurrent and accounts for 20% of all the reported mutations, whereas all others are private. Most mutations are clustered in the two major functional domains, the helicase and the PHD-like domain. So far, no clear genotype-phenotype correlation has been established, with exception to the rare truncating mutations located at the C-terminal part of the protein, which are consistently associated with severe urogenital defects. In this study, we report the molecular analysis performed in 16 families positive for ATRX. Our findings indicate that, in addition to the previously described mutation 'hotspot' in the PHD-like domain, two other protein sections emerge as minor 'hotspots' in the helicase region encoded by exons 18-20 and 26-29, respectively, gathering 33% of all described mutations. Additionally, based on the clinical data collected for 22 patients from the 16 families, we observe that mutations in the PHD-like domain produce severe and permanent psychomotor deficiency, usually preventing patients from walking, as well as constant urogenital abnormalities, while mutations in the helicase domain lead to delayed but correct psychomotor acquisitions together with mild or absent urogenital abnormalities. In summary, mutations in the helicase domain are associated with milder phenotypes than mutations in the PHD-like domain.
机译：ATRX中的突变与X连锁智力低下综合征的广泛且临床异质性谱有关。参与染色质重塑的ATRX蛋白属于SWI / SNF DNA解旋酶家族，并含有植物同源结构域（PHD）样结构域。迄今为止，ATRX已报告了60多种不同的突变。其中之一是复发性的，占所有报道的突变的20％，而其他所有突变都是私人的。大多数突变聚集在两个主要功能域中，解旋酶和PHD样域。到目前为止，除了位于蛋白质C端的罕见截断突变（与严重的泌尿生殖系统缺陷一致相关）外，尚未建立明确的基因型与表型相关性。在这项研究中，我们报告了在ATRX阳性的16个家族中进行的分子分析。我们的发现表明，除了先前描述的PHD样结构域中的突变“热点”外，其他两个蛋白质部分在分别由外显子18-20和26-29编码的解旋酶区域中以次要的“热点”出现，所有描述的突变中有33％。此外，根据从16个家庭的22位患者收集的临床数据，我们观察到PHD样结构域中的突变会产生严重的永久性精神运动缺陷，通常会阻止患者行走以及持续的泌尿生殖道异常，而解旋酶域导致延迟但正确的精神运动性获取，以及轻度或无泌尿生殖道异常。总之，解旋酶结构域中的突变与比PHD样结构域中的突变具有更轻的表型相关。

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