Centre for Rare Diseases and Personalised Medicine, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
J Med Genet. 2013 Sep;50(9):635-9. doi: 10.1136/jmedgenet-2013-101693. Epub 2013 Jun 28.
About half of all children with a clinical diagnosis of Silver-Russell syndrome (SRS) have a detectable molecular genetic abnormality (maternal uniparental disomy of chromosome upd(7)mat or hypomethylation of H19 differentially methylated region (DMR). The selection of children for molecular genetic testing can be difficult for non-specialists because of the broad phenotypic spectrum of SRS and the tendency of the facial features to mitigate during late childhood. Several clinical scoring systems for SRS have been developed by specialist researchers, but the utility of these for guiding molecular genetic testing in routine clinical practice has not been established.
To evaluate the utility of four published clinical scoring systems for genetic testing in a cohort of patients referred to a clinical service laboratory.
Individuals with suspected SRS referred for molecular genetic testing of H19 DMR methylation status or upd(7)mat.
36 of 139 (25.9%) patients referred for testing had a genetic abnormality identified. Comparison of four published clinical scoring systems demonstrated that all included subjective criteria that could be difficult for the general clinician to assess. We developed a novel, simplified, scoring system utilising four objective, easily measured parameters that performed similarly to the most sensitive and specific published scoring system.
Effective utilisation of genetic testing by clinicians without specialist clinical genetics training will be facilitated by the development of targeted testing protocols that are based on robust objective clinical features and are designed for use in a busy clinical practice rather than a research setting.
大约一半有临床诊断为 Silver-Russell 综合征（SRS）的儿童存在可检测的分子遗传异常（母源单亲二倍体染色体 upd(7)mat 或 H19 差异甲基化区（DMR）低甲基化）。由于 SRS 的表型谱广泛，并且面部特征在儿童后期趋于减轻，因此非专家选择儿童进行分子遗传学检测可能具有挑战性。一些专家研究人员已经开发了用于 SRS 的几种临床评分系统，但尚未确定这些系统在常规临床实践中指导分子遗传学检测的实用性。
评估四个已发表的临床评分系统在转介至临床服务实验室的患者队列中进行基因检测的实用性。
疑似 SRS 的个体转介进行 H19 DMR 甲基化状态或 upd(7)mat 的分子遗传学检测。
在 139 名接受检测的患者中，有 36 名发现存在遗传异常。对四个已发表的临床评分系统进行比较表明，所有系统均包含主观标准，普通临床医生可能难以评估。我们开发了一种新的、简化的评分系统，利用四个客观、易于测量的参数，其性能与最敏感和最特异的已发表评分系统相似。
对于没有专业临床遗传学培训的临床医生，通过开发基于可靠客观临床特征的靶向检测方案，并设计用于繁忙的临床实践而不是研究环境，将有助于有效地利用遗传检测。
