Gécz J, Oostra B A, Hockey A, Carbonell P, Turner G, Haan E A, Sutherland G R, Mulley J C
Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, Adelaide, Australia.
Hum Mol Genet. 1997 Mar;6(3):435-41. doi: 10.1093/hmg/6.3.435.
Normal individuals express the two alternative transcripts, FMR2 and Ox19, from the FRAXE-associated CpG island. Molecular analysis of the Ox19 transcript suggests that it is a truncated isoform of the FMR2 gene with an alternative 3' end. Both isoforms showed a similar pattern of expression, with the Ox19 isoform expressed at a much lower level. Fibroblasts, chorionic villi and hair roots showed the highest level of FMR2 expression, whole blood cells and amniocytes showed very low expression, and the transcript was not detected in lymphoblasts. Fibroblasts of 11 individuals from seven families segregating FRAXE were assayed for FMR2 expression and FRAXE CpG island methylation. A man with an unmethylated expansion of 0.6 kb expressed FMR2 and represents a pre-mutation carrier. All chromosomes with FRAXE CCG expansions of 0.8 kb or greater were fully methylated and did not express the FMR2 gene, analogous to the mechanism of silencing the FMR1 gene in carriers of the FRAXA full mutation. The boundary between FRAXE pre-mutation and FRAXE full mutation is between 0.7 and 0.8 kb. Two men with absence of FMR2 expression in fibroblasts were not mentally impaired, suggesting that IQ in some men with FRAXE full mutation may remain within the normal range. Although molecular tools to study FRAXE non-specific mental retardation are now available, further psychometric and molecular studies are needed to characterize the effect of the FRAXE full mutation for the purpose of genetic counselling.
正常个体表达来自FRAXE相关CpG岛的两种可变转录本，即FMR2和Ox19。对Ox19转录本的分子分析表明，它是FMR2基因的一种截短异构体，具有可变的3'末端。两种异构体表现出相似的表达模式，其中Ox19异构体的表达水平要低得多。成纤维细胞、绒毛膜绒毛和发根显示出最高水平的FMR2表达，全血细胞和羊膜细胞显示出极低的表达，并且在淋巴母细胞中未检测到该转录本。对来自7个分离FRAXE的家系的11名个体的成纤维细胞进行了FMR2表达和FRAXE CpG岛甲基化检测。一名具有0.6 kb未甲基化扩增的男性表达FMR2，代表前突变携带者。所有具有0.8 kb或更大的FRAXE CCG扩增的染色体均完全甲基化，不表达FMR2基因，这类似于FRAXA全突变携带者中FMR1基因沉默的机制。FRAXE前突变和FRAXE全突变之间的界限在0.7至0.8 kb之间。两名成纤维细胞中无FMR2表达的男性没有智力障碍，这表明一些FRAXE全突变男性的智商可能仍在正常范围内。尽管现在已有研究FRAXE非特异性智力迟钝的分子工具，但为了遗传咨询的目的，仍需要进一步的心理测量和分子研究来表征FRAXE全突变的影响。
