Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Prenat Diagn. 2011 Oct;31(10):925-31. doi: 10.1002/pd.2815. Epub 2011 Jun 30.
To determine risks of expansion for normal, intermediate, and premutation FMR1 CGG repeats.
PCR was used to compare the FMR1 alleles in prenatal (chorionic villi and amniocytes) and parental samples collected from 1991 to 2010. Prenatal diagnoses were confirmed by Southern analysis.
Fragile X analysis of 1112 pregnancies identified 558 normal, 106 intermediate, 216 premutation, and 232 full mutation fetuses. Of 509 maternal, intermediate, and premutation alleles, 350 (68.7%) were unstable on transmission with expansions ranging from one repeat to the full mutation. The smallest premutation alleles expanding to the full mutation were in mothers with 65 and 66 repeats. Transmissions from women with or without a family history of fragile X suggested greater instability in women from families that included full mutation expansions.
The maternal transmissions of alleles with 55 to 59 CGG repeats summarized here indicate that the risk for expansion to full mutation is substantially less than previous estimates for this size category. Most premutation alleles with no family history of fragile X exhibited less instability than those with a history of fragile X. Thus, lower risk estimates for full mutation expansion may be appropriate for women newly identified as premutation carriers through routine screening.
确定正常、中间和前突变 FMR1 CGG 重复的扩展风险。
PCR 用于比较 1991 年至 2010 年间收集的产前（绒毛膜和羊水细胞）和父母样本中的 FMR1 等位基因。产前诊断通过 Southern 分析确认。
对 1112 例妊娠进行脆性 X 分析，确定了 558 例正常、106 例中间、216 例前突变和 232 例全突变胎儿。在 509 个母亲、中间和前突变等位基因中，有 350 个（68.7%）在传递过程中不稳定，重复数从一个增加到全突变。扩展到全突变的最小前突变等位基因存在于重复数为 65 和 66 的母亲中。来自脆性 X 家族史有或无的女性的传递表明，包括全突变扩展的家族中的女性更不稳定。
这里总结的 55 至 59 个 CGG 重复的母体等位基因传递表明，扩展到全突变的风险明显低于之前对该大小类别的估计。大多数没有脆性 X 家族史的前突变等位基因的不稳定性低于有脆性 X 家族史的等位基因。因此，对于通过常规筛查新发现为前突变携带者的女性，全突变扩展的风险估计可能较低。
