Ramos F J, Eunpu D L, Finucane B, Pfendner E G
Department of Pediatrics, Albert Einstein Medical Center, Philadelphia, PA.
Am J Dis Child. 1993 Nov;147(11):1231-5. doi: 10.1001/archpedi.1993.02160350105016.
The recent identification of an abnormally amplified trinucleotide (cytosine guanine guanine) repeat in the fragile X gene (FMR-1) of males with fragile X syndrome and their carrier mothers allows the study of the mutation in individuals at risk. In this report, data on 396 patients and 35 normal controls are reported. Included in this sample are patients with no known family history of fragile X syndrome or mental retardation for whom the risks of fragile X syndrome are unclear. All 39 cytogenetically positive affected males and six females had the full mutation, as represented by a restriction fragment size increase (delta) of 500 base pairs (bp) or more within the cytosine guanine guanine repeat-bearing fragment of the FMR-1 gene; and all 16 of the normal obligate carrier females bore the premutation, as demonstrated by a delta of 100 to 500 bp. Of 124 patients (62 males and 62 females) with a family history of fragile X syndrome, five (8%) of the males and 25 (40%) of the females had the premutation. Five (2.2%) of the 231 mentally impaired patients with no confirmed family history of fragile X syndrome were found to have the full mutation. Twelve (33%) of 36 mentally impaired males and one (20%) of five females with unknown family history were found to carry an amplified cytosine guanine guanine repeat. Using this technique, we also reevaluated risk assessments previously generated by linkage analysis and unambiguously determined the carrier status of individual family members.
最近在患有脆性X综合征的男性及其携带者母亲的脆性X基因（FMR-1）中发现了异常扩增的三核苷酸（胞嘧啶-鸟嘌呤-鸟嘌呤）重复序列，这使得对有患病风险个体的该突变进行研究成为可能。在本报告中，报告了396例患者和35例正常对照的数据。该样本包括无脆性X综合征或智力迟钝家族史且脆性X综合征风险不明的患者。所有39例细胞遗传学检测呈阳性的受影响男性和6例女性均有完全突变，表现为FMR-1基因含胞嘧啶-鸟嘌呤-鸟嘌呤重复序列的片段内限制性片段大小增加（δ）500个碱基对（bp）或更多；所有16例正常的必然携带者女性均有前突变，表现为δ为100至500 bp。在有脆性X综合征家族史的124例患者（62例男性和62例女性）中，5例（8%）男性和25例（40%）女性有前突变。在231例无脆性X综合征确诊家族史的智力障碍患者中，5例（2.2%）有完全突变。在36例家族史不明的智力障碍男性中，12例（33%）和5例女性中的1例（20%）被发现携带扩增的胞嘧啶-鸟嘌呤-鸟嘌呤重复序列。使用该技术，我们还重新评估了先前通过连锁分析得出的风险评估，并明确确定了个体家庭成员的携带者状态。
