The Central Laboratory of Birth Defects Prevention and Control, The Affiliated Women and Children's Hospital of Ningbo University, Ningbo, China; Ningbo Key Laboratory for the Prevention and Treatment of Embryogenic Diseases, The Affiliated Women and Children's Hospital of Ningbo University, Ningbo, China; Ningbo Key Laboratory of Genomic Medicine and Birth Defects Prevention, The Affiliated Women and Children's Hospital of Ningbo University, Ningbo, China.
Liangzhu Laboratory, Zhejiang University, Hangzhou, China.
Clin Immunol. 2024 Dec;269:110394. doi: 10.1016/j.clim.2024.110394. Epub 2024 Oct 29.
Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease characterised by early onset stroke, recurrent fever, and diverse vascular pathologies, caused by loss-of-function homozygous or compound heterozygous variants of ADA2. This research aimed to determine the carrier frequency and expected incidence of DADA2 in China, using massive exome sequencing (ES) data. A total of 50 likely pathogenic/pathogenic variants (LP/PVs) were identified among 69,413 Chinese individuals, including 20 novel and rare variants (<0.0022 % allele frequency), expanding the known spectrum of PVs in ADA2. The overall carrier frequency in the Chinese population was 1.05 % (732/69,413) and the estimated incidence of DADA2 was approximately one in 92,251 individuals. The present study provides an accurate estimation of the prevalence of DADA2 in China, supporting genetic counseling, early diagnosis treatment, and prognostic evaluation.
腺苷脱氨酶 2 缺乏症(DADA2)是一种常染色体隐性自身炎症性疾病,其特征为早发性卒中、反复发热以及多种血管病变,由 ADA2 的功能丧失性纯合子或复合杂合子变异引起。本研究旨在利用大规模外显子组测序(ES)数据,确定中国人群中 DADA2 的携带频率和预期发病率。在 69413 名中国个体中,共鉴定出 50 种可能的致病性/致病性变异(LP/PV),包括 20 种新的罕见变异(<0.0022%等位基因频率),扩大了 ADA2 中已知的 PV 谱。中国人群的总体携带频率为 1.05%(732/69413),DADA2 的估计发病率约为每 92251 人中有 1 人。本研究为中国 DADA2 的流行率提供了准确的估计,支持遗传咨询、早期诊断和治疗以及预后评估。