Wotton Tiffany, Wiley Veronica, Bennetts Bruce, Christie Louise, Wilcken Bridget, Jenkins Gemma, Rogers Carolyn, Boyle Jackie, Field Michael
The NSW Newborn Screening Programme, The Children's Hospital at Westmead, Westmead, NSW 2145, Australia.
Disciplines of Paediatrics & Child Health and Genetic Medicine, The University of Sydney, Sydney, NSW 2006, Australia.
Int J Neonatal Screen. 2018 Feb 13;4(1):9. doi: 10.3390/ijns4010009. eCollection 2018 Mar.
Fragile X syndrome (FXS) is the most prevalent heritable cause of cognitive impairment but is not yet included in a newborn screening (NBS) program within Australia. This paper aims to assess the feasibility and reliability of population screening for FXS using a pilot study in one hospital. A total of 1971 mothers consented for 2000 newborns to be tested using routine NBS dried blood spot samples. DNA was extracted and a modified PCR assay with a chimeric CGG primer was used to detect fragile X alleles in both males and females in the normal, premutation, and full mutation ranges. A routine PCR-based fragile X assay was run in parallel to validate the chimeric primer assay. Babies with CGG repeat number ≥59 were referred for family studies. One thousand nine hundred and ninety NBS samples had a CGG repeat number less than 55 (1986 < 50); 10 had premutation alleles >54 CGG repeats (1/123 females and 1/507 males). There was complete concordance between the two PCR-based assays. A recent review revealed no clinically identified cases in the cohort up to 5 years later. The cost per test was $AUD19. Fragile X status can be determined on routine NBS samples using the chimeric primer assay. However, whilst this assay may not be considered cost-effective for population screening, it could be considered as a second-tier assay to a developed immunoassay for fragile X mental retardation protein (FMRP).
脆性X综合征（FXS）是认知障碍最常见的遗传性病因，但澳大利亚的新生儿筛查（NBS）项目中尚未包含该疾病。本文旨在通过在一家医院开展的试点研究，评估对FXS进行人群筛查的可行性和可靠性。共有1971位母亲同意对2000名新生儿使用常规NBS干血斑样本进行检测。提取DNA，并使用带有嵌合CGG引物的改良PCR检测法来检测正常、前突变和全突变范围内男性和女性的脆性X等位基因。同时进行基于常规PCR的脆性X检测以验证嵌合引物检测法。CGG重复数≥59的婴儿被转诊进行家系研究。1990份NBS样本的CGG重复数小于55（1986份<50）；10份样本有>54个CGG重复的前突变等位基因（1/123名女性和1/507名男性）。两种基于PCR的检测方法结果完全一致。最近的一项综述显示，在长达5年的随访期内，该队列中未发现临床确诊病例。每次检测的成本为19澳元。使用嵌合引物检测法可在常规NBS样本上确定脆性X状态。然而，虽然该检测法对于人群筛查可能不具有成本效益，但可考虑将其作为针对脆性X智力低下蛋白（FMRP）的成熟免疫检测法的二线检测方法。
