Siitonen H Annika, Sotkasiira Jenni, Biervliet Martine, Benmansour Abdelmadjid, Capri Yline, Cormier-Daire Valerie, Crandall Barbara, Hannula-Jouppi Katariina, Hennekam Raoul, Herzog Denise, Keymolen Kathelijn, Lipsanen-Nyman Marita, Miny Peter, Plon Sharon E, Riedl Stefan, Sarkar Ajoy, Vargas Fernando R, Verloes Alain, Wang Lisa L, Kääriäinen Helena, Kestilä Marjo
Department of Molecular Medicine, National Public Health Institute and FIMM, Institute for Molecular Medicine Finland, Helsinki, Finland.
Eur J Hum Genet. 2009 Feb;17(2):151-8. doi: 10.1038/ejhg.2008.154. Epub 2008 Aug 20.
Mutations in the RECQL4 gene can lead to three clinical phenotypes with overlapping features. All these syndromes, Rothmund-Thomson (RTS), RAPADILINO and Baller-Gerold (BGS), are characterized by growth retardation and radial defects, but RAPADILINO syndrome lacks the main dermal manifestation, poikiloderma that is a hallmark feature in both RTS and BGS. It has been previously shown that RTS patients with RECQL4 mutations are at increased risk of osteosarcoma, but the precise incidence of cancer in RAPADILINO and BGS has not been determined. Here, we report that RAPADILINO patients identified as carriers of the c.1390+2delT mutation (p.Ala420_Ala463del) are at increased risk to develop lymphoma or osteosarcoma (6 out of 15 patients). We also summarize all the published RECQL4 mutations and their associated cancer cases and provide an update of 14 novel RECQL4 mutations with accompanying clinical data.
RECQL4基因的突变可导致三种具有重叠特征的临床表型。所有这些综合征，即罗思蒙德-汤姆森综合征（RTS）、拉帕迪利诺综合征和巴勒-杰罗尔德综合征（BGS），都以生长发育迟缓及桡骨缺陷为特征，但拉帕迪利诺综合征缺乏主要的皮肤表现——皮肤异色症，而皮肤异色症是RTS和BGS的标志性特征。先前研究表明，携带RECQL4基因突变的RTS患者患骨肉瘤的风险增加，但拉帕迪利诺综合征和BGS患者的确切癌症发病率尚未确定。在此，我们报告，被鉴定为携带c.1390+2delT突变（p.Ala420_Ala463del）的拉帕迪利诺综合征患者患淋巴瘤或骨肉瘤的风险增加（15名患者中有6名）。我们还总结了所有已发表的RECQL4基因突变及其相关癌症病例，并提供了14个新的RECQL4基因突变及其临床数据的更新情况。
