Orrico A, Galli L, Dotti M T, Plewnia K, Censini S, Federico A
Department of Molecular Biology, Medical Genetics, Università degli Studi di Siena, Italy.
Am J Med Genet. 1998 Jul 24;78(4):341-4.
The main mutation in fragile X patients is the expansion of the CGG repeat in the first exon of the FMR1 gene, associated with hypermethylation of the proximal CpG island. An increasing number of atypical cases have been reported showing the coexistence of full mutation and premutated or normal-sized alleles. These genotypes are more difficult to detect, and if a PCR strategy alone is adopted, they can be incorrectly identified. We report on a fragile X man with severe phenotype and mosaicism for full mutation and a (CGG)7 normal allele, the shortest fragment reported as yet in mosaics. This case of mosaicism, as other similar cases previously reported, suggests that the normal-length allele can derive from a deletion during the same early stage of development in which the full mutation expansion also arose.
脆性X综合征患者的主要突变是FMR1基因第一外显子中CGG重复序列的扩增，这与近端CpG岛的高甲基化有关。越来越多的非典型病例被报道，显示出全突变与前突变或正常大小等位基因共存。这些基因型更难检测，如果仅采用PCR策略，可能会被错误识别。我们报告了一例具有严重表型且存在全突变和（CGG）7正常等位基因嵌合体的脆性X男性患者，这是迄今报道的嵌合体中最短的片段。与之前报道的其他类似病例一样，这例嵌合体病例表明，正常长度的等位基因可能源于与全突变扩增相同的早期发育阶段的缺失。
