基于人群的新生儿筛查中，反复性 22q11.2 缺失的当代活产儿患病率估计：一项横断面分析。
Estimate of the contemporary live-birth prevalence of recurrent 22q11.2 deletions: a cross-sectional analysis from population-based newborn screening.
机构信息
Clinical Genetics Research Program (Blagojevic, Heung, Bassett), Centre for Addiction and Mental Health; The Dalglish Family 22q Clinic (Blagojevic, Heung, Bassett), University Health Network; Department of Psychiatry (Bassett), University of Toronto, Toronto, Ont.; Children's Hospital of Eastern Ontario Research Institute (Theriault, Chakraborty, Kernohan, Bulman), University of Ottawa, Ottawa, Ont.; Division of Pediatric Cardiothoracic Surgery (Tomita-Mitchell), Department of Surgery, Medical College of Wisconsin, Herma Heart Institute, Milwaukee, Wisc.
出版信息
CMAJ Open. 2021 Aug 17;9(3):E802-E809. doi: 10.9778/cmajo.20200294. Print 2021 Jul-Sep.
BACKGROUND
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.
METHODS
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.
RESULTS
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, < 0.001).
INTERPRETATION
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.
背景
尽管致病性 22q11.2 缺失是导致发育迟缓及终身疾病负担的重要原因之一，但由于其临床表现存在变异性和复杂性，导致漏诊、分子诊断延迟，以及发病频率不确定。本研究旨在通过基于人群的新生儿筛查样本，估计典型 22q11.2 缺失的当代活产患病率，并分析相关临床表现的数据。
方法
本研究利用 2017 年 1 月至 2018 年 9 月期间，在安大略省收集的大约 12%的所有干血斑中，利用 DNA 样本进行前瞻性筛查，使用多重定量聚合酶链反应检测 22q11.2 缺失，并进行独立的确认性研究。本研究利用横断面分析比较了有和无 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。
结果
根据总共筛查的 30074 个样本，估计 22q11.2 缺失的最小患病率为每 10000 例活产中 1 例（95%置信区间[CI]每 10000 例 2.5 至 7.8 例），其中 14 例经证实存在 22q11.2 缺失。在足月单胎中，22q11.2 缺失的样本中位母亲年龄明显更年轻（25.5 岁 vs. 32.0 岁，差值为 6.5 岁，95%CI 为 7 至 2 岁），更小比例的样本出生体重低于胎龄（比值比 7.00，95%CI 为 2.36 至 23.18），TREC 水平中位数更低（108.9 拷贝/3 μL vs. 602.5 拷贝/3 μL， < 0.001）。
结论
这些结果表明，22q11.2 缺失综合征是最常见的罕见遗传疾病之一，可能与相对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期诊断的公共卫生重要性，这将能够及时筛查和管理与 22q11.2 缺失相关的明确可采取的特征。
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