Department of Pediatrics, Daegu Catholic University School of Medicine, Daegu, South Korea.
Department of Laboratory Medicine, Green Cross Genome, Yong-in, South Korea.
J Hum Genet. 2020 Jun;65(6):551-555. doi: 10.1038/s10038-020-0735-9. Epub 2020 Mar 6.
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability, especially in males. Females with FXS tend to be relatively mildly affected because of compensation by a second X chromosome with a normal FMR1 gene. In most cases, FXS is caused by an expansion of the CGG repeats (>200 triplets, full mutation, FM) in the 5'-untranslated region of the FMR1 gene. Premutation alleles (PM, 55-200 repeats), usually lack the clinical features of FXS, are highly unstable when transmitted to offspring and can give rise to FM, especially in female meiosis. We describe a 3-year-old girl with typical FXS, with only a fully expanded FMR1 allele (288 CGG repeats) due to uniparental isodisomy of X chromosome, inherited from mother carrying a premutation allele. The patient's FMR1 methylation region is completely methylated due to full mutation of CGG repeat. This unusual and rare case indicates the importance of a detailed genomic approach to explain nontraditional Mendelian inheritance pattern.
脆性 X 综合征（FXS）是最常见的遗传性智力障碍病因，尤其在男性中。由于携带正常 FMR1 基因的另一条 X 染色体的补偿作用，FXS 女性患者的症状往往相对较轻。在大多数情况下，FXS 是由 FMR1 基因 5'-非翻译区的 CGG 重复扩增（>200 个三联体，完全突变，FM）引起的。前突变等位基因（PM，55-200 个重复）通常缺乏 FXS 的临床特征，在传递给后代时极不稳定，并且可能导致 FM，尤其是在女性减数分裂中。我们描述了一例 3 岁女孩，具有典型的 FXS，仅携带一个完全扩增的 FMR1 等位基因（288 个 CGG 重复），这是由于来自携带前突变等位基因的母亲的 X 染色体单亲二体性所致。由于 CGG 重复完全突变，患者的 FMR1 甲基化区域完全甲基化。这种不常见且罕见的情况表明，详细的基因组方法对于解释非传统孟德尔遗传模式非常重要。
