Estimate of the contemporary live-birth prevalence of recurrent 22q11.2 deletions: a cross-sectional analysis from population-based newborn screening.
Estimate of the contemporary live-birth prevalence of recurrent 22q11.2 deletions: a cross-sectional analysis from population-based newborn screening.
复制标题
DOI：
10.9778/cmajo.20200294
复制
发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Bassett AS
中科院分区：
文献类型：
--
作者：
Blagojevic C;Heung T;Theriault M;Tomita-Mitchell A;Chakraborty P;Kernohan K;Bulman DE;Bassett AS
尽管致病性 22q11.2 缺失是发育迟缓和终生疾病负担的重要原因，但其可变且复杂的临床表达导致认识不足、分子诊断延迟和患病率不确定。我们试图使用基于人群的新生儿筛查样本来估计典型 22q11.2 缺失的当代活产患病率，并检查可用于相关临床特征的数据。我们使用从 2017 年 1 月至 2018 年 9 月期间在安大略省收集的用于新生儿筛查的所有干血点中约 12% 的无偏见样本中获得的 DNA，使用多重定量聚合酶链反应测定前瞻性筛查 22q11.2 缺失，并进行独立验证性研究。我们使用横断面分析来比较具有和不具有 22q11.2 缺失的样本之间可用的临床和 T 细胞受体切除环（TREC，用于新生儿筛查严重联合免疫缺陷）数据。根据总共筛选的 30 074 个样本，估计 22q11.2 缺失的最低患病率为 2148 例（每 10 000 例 4.7 例）活产中 1 例（95% 置信区间 [CI] 为每 10 000 例 2.5 至 7.8 例），其中 14 例已确认 22q11.2 缺失。在足月单胎中，22q11.2 缺失的样本中位母亲年龄显着更年轻（25.5 岁 vs. 32.0 岁，差异 -6.5 岁，95% CI -7 至 -2 岁），出生体重小于胎龄的比例更大（比值比 7.00，95% CI 2.36 至 23.18），中位 TREC 水平较低（108.9 岁 vs. 108.9 岁）。 602.5 拷贝/3 μL，p < 0.001）。这些结果表明，22q11.2 缺失综合征是最常见的罕见遗传病之一，可能与相对较年轻的母亲年龄和产前生长异常有关。这些发现支持了早期（产前和新生儿）诊断对公共卫生的重要性，这将有助于及时筛查和管理与 22q11.2 缺失相关的众所周知的可操作特征。
Although pathogenic 22q11.2 deletions are an important cause of developmental delays and lifelong disease burden, their variable and complex clinical expression contributes to under-recognition, delayed molecular diagnosis and uncertainty about prevalence. We sought to estimate the contemporary live-birth prevalence of typical 22q11.2 deletions using a population-based newborn screening sample and to examine data available for associated clinical features. Using DNA available from an unbiased sample of about 12% of all dried blood spots collected for newborn screening in Ontario between January 2017 and September 2018, we prospectively screened for 22q11.2 deletions using multiplex quantitative polymerase chain reaction assays and conducted independent confirmatory studies. We used cross-sectional analyses to compare available clinical and T-cell receptor excision circle (TREC, used in newborn screening for severe combined immunodeficiency) data between samples with and without 22q11.2 deletions. The estimated minimum prevalence of 22q11.2 deletions was 1 in 2148 (4.7 per 10 000) live births (95% confidence interval [CI] 2.5 to 7.8 per 10 000), based on a total of 30 074 samples screened, with 14 having confirmed 22q11.2 deletions. Of term singletons, samples with 22q11.2 deletions had significantly younger median maternal age (25.5 v. 32.0 yr, difference −6.5 yr, 95% CI −7 to −2 yr), a greater proportion with small birth weight for gestational age (odds ratio 7.00, 95% CI 2.36 to 23.18) and lower median TREC levels (108.9 v. 602.5 copies/3 μL, p < 0.001). These results indicate that the 22q11.2 deletion syndrome is one of the most common of rare genetic conditions and may be associated with relatively younger maternal ages and with prenatal growth abnormalities. The findings support the public health importance of early — prenatal and neonatal — diagnosis that would enable prompt screening for and management of well-known actionable features associated with 22q11.2 deletions.