Rothmund-Thomson syndrome and RECQL4 defect: Splitting and lumping
Rothmund-Thomson syndrome and RECQL4 defect: Splitting and lumping
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DOI：
10.1016/j.canlet.2005.07.042
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发表时间：
2006-01-28
期刊：
影响因子：
9.7
通讯作者：
Roversi, G
中科院分区：
文献类型：
--
作者：
Larizza, L;Magnani, I;Roversi, G
罗斯蒙德-汤姆森综合征 (RTS) 是一种罕见的常染色体隐性遗传性皮肤病，具有异质性临床特征。编码 RecQ DNA 解旋酶的 RECQL4 突变存在于大部分（但并非所有临床诊断患者）中，因此可以将 RTS 归类为 RecQ 解旋酶染色体不稳定缺陷，包括 Bloom 综合征和 Werner 综合征。 RECQL4 测试的结果与可变的临床表现相结合，有利于将 RTS 临床表型分解为不同遗传控制下的疾病实体。与此同时，将 RECQL4 基因与其他两种疾病（RAPADILINO 和 Baller-Gerold）集中在一起，为揭示等位基因异质性复杂的基因型-表型相关性铺平了道路。 Recql4 敲除小鼠为理解 RECQL4 解旋酶的功能作用提供了重要的见解，这已通过 RECQL4 蛋白及其作用途径的初始生化特征以及对酵母和非洲爪蟾中 RECQL4 同源物的研究得到证实。 RECQL4 在 DNA 复制起始和姐妹染色单体凝聚力中的作用已被提出，目前与通过不同方法获得的证据相符。需要进一步的工作来定义 RECQL4 与其他 RecQ 解旋酶相关的特定和共享功能，并将 RECQL4 疾病与其他具有出生缺陷和癌症倾向的基因组不稳定综合征联系起来。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
Rothmund-Thomson Syndrome (RTS) is a rare autosomal recessive genodermatosis with a heterogeneous clinical profile. Mutations in RECQL4, encoding a RecQ DNA helicase, are present in a large fraction, but not all clinically diagnosed patients, allowing to classify RTS among the RecQ helicase chromosomal instability defects including Bloom's and Werner's syndromes. Results of RECQL4 test coupled to the variable clinical presentation favored the splitting of RTS clinical phenotype into nosological entities under distinct genetic control. In parallel, lumping of the RECQL4 gene to two other diseases, RAPADILINO and Baller-Gerold has paved the way to unravel through allelic heterogeneity complex genotype-phenotype correlations. Recql4 knockout mice provided crucial insights into the comprehension of the functional role of RECQL4 helicase, which have been corroborated by the initial biochemical characterization of RECQL4 protein and its acting pathway and by studies on RECQL4 homologs in yeast and Xenopus. A role for RECQL4 in initiation of DNA replication and in sister chromatid cohesion has been proposed, which currently fits the pieces of evidence achieved by different approaches. Further work is needed to define the specific and shared functions of RECQL4 in relation to other RecQ helicases and to connect RECQL4 diseases to other genomic instability syndromes with birth defects and cancer predisposition. (c) 2005 Elsevier Ireland Ltd. All rights reserved.