Frints Suzanna G M, Jun Lin, Fryns Jean-Pierre, Devriendt Koen, Teulingkx Rudi, Van den Berghe Lut, De Vos Bernice, Borghgraef Martine, Chelly Jamel, Des Portes Vincent, Van Bokhoven Hans, Hamel Ben, Ropers Hans-Hilger, Kalscheuer Vera, Raynaud Martine, Moraine Claude, Marynen Peter, Froyen Guy
Human Genome Laboratory and Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium.
Am J Med Genet A. 2003 Jun 15;119A(3):367-74. doi: 10.1002/ajmg.a.20195.
We describe a 59-year-old male (patient A059) with moderate to severe mental retardation (MR) and a pericentric inversion of the X-chromosome: inv(X)(p21.1;q22.1). He had short stature, pectus excavatum, general muscle wasting, and facial dysmorphism. Until now, no other patients with similar clinical features have been described in the literature. Molecular analysis of both breakpoints led to the identification of a novel "Nuclear RNA export factor" (NXF) gene cluster on Xq22.1. Within this cluster, the NXF5 gene was interrupted with subsequent loss of gene expression. Hence, mutation analysis of the NXF5 and its neighboring homologue, the NXF2 gene was performed in 45 men with various forms of syndromic X-linked MR (XLMR) and in 70 patients with nonspecific XLMR. In the NXF5 gene four nucleotide changes: one intronic, two silent, and one missense (K23E), were identified. In the NXF2 gene two changes (one intronic and one silent) were found. Although none of these changes were causative mutations, we propose that NXF5 is a good candidate gene for this syndromic form of XLMR, given the suspected role of NXF proteins is within mRNA export/transport in neurons. Therefore, mutation screening of the NXF gene family in phenotypically identical patients is recommended.
我们描述了一名59岁男性（患者A059），患有中度至重度智力发育迟缓（MR）且存在X染色体臂间倒位：inv(X)(p21.1;q22.1)。他身材矮小、有漏斗胸、全身肌肉萎缩且面部畸形。迄今为止，文献中尚未描述过其他具有类似临床特征的患者。对两个断点进行分子分析后，在Xq22.1上鉴定出一个新的“核RNA输出因子”（NXF）基因簇。在这个基因簇中，NXF5基因被打断，随后基因表达缺失。因此，对45名患有各种形式综合征性X连锁智力发育迟缓（XLMR）的男性以及70名患有非特异性XLMR的患者进行了NXF5及其相邻同源基因NXF2的突变分析。在NXF5基因中鉴定出四个核苷酸变化：一个内含子变化、两个沉默变化和一个错义变化（K23E）。在NXF2基因中发现了两个变化（一个内含子变化和一个沉默变化）。尽管这些变化均不是致病突变，但考虑到NXF蛋白在神经元mRNA输出/运输中的推测作用，我们认为NXF5是这种综合征性XLMR的一个良好候选基因。因此，建议对表型相同的患者进行NXF基因家族的突变筛查。
