Department of Pediatrics and Pediatric Neurology, Georg August University, Göttingen, Germany.
Am J Med Genet A. 2011 Aug;155A(8):2003-7. doi: 10.1002/ajmg.a.34122. Epub 2011 Jul 7.
Alterations of the Fragile Mental Retardation 2 gene (FMR2, synonym AFF2) can result in non-specific, mild to borderline X-linked intellectual disability (XLID), and behavioral problems. The well-known molecular pathomechanism of this condition, also referred to as FRAXE, is a (CCG)(n) trinucleotide repeat expansion which leads to silencing of the FMR2 gene. However, deletions within the FMR2 gene may also be causative of the disorder. Here, we report on two brothers diagnosed with FRAXE in whom a small deletion in the FMR2 gene was detected by whole genome array comparative genomic hybridization (CGH). The deletion was also present in their clinically healthy mother and maternal uncle who was similarly affected, but not in a healthy older brother of the two patients. Our observation demonstrates that FMR2 gene deletions may contribute to the FRAXE phenotype. Therefore, we suggest that screening for FMR2 gene deletions using array CGH should be considered in patients with non-specific XLID and absent trinucleotide expansion.
脆性智力低下 2 号基因（FMR2，同义词 AFF2）的改变可导致非特异性、轻度至边缘性 X 连锁智力障碍（XLID）和行为问题。这种情况也被称为 FRAXE 的众所周知的分子发病机制是（CCG）（n）三核苷酸重复扩展，导致 FMR2 基因沉默。然而，FMR2 基因内的缺失也可能是该疾病的原因。在这里，我们报告了两名被诊断为 FRAXE 的兄弟，他们的 FMR2 基因中存在小的缺失，这是通过全基因组阵列比较基因组杂交（CGH）检测到的。该缺失也存在于他们临床健康的母亲和受影响的姨父中，但不存在于这两个患者的健康的哥哥中。我们的观察表明，FMR2 基因缺失可能导致 FRAXE 表型。因此，我们建议在非特异性 XLID 和不存在三核苷酸扩展的患者中，使用阵列 CGH 筛查 FMR2 基因缺失。
