High Prevalence of a Monogenic Cause in Han Chinese Diagnosed With Type 1 Diabetes, Partly Driven by Nonsyndromic Recessive WFS1 Mutations
High Prevalence of a Monogenic Cause in Han Chinese Diagnosed With Type 1 Diabetes, Partly Driven by Nonsyndromic Recessive WFS1 Mutations
复制标题
被诊断为 1 型糖尿病的汉族人中单基因病因的患病率很高，部分原因是非综合征性隐性 WFS1 突变
DOI：
10.2337/db19-0510
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发表时间：
2020-01-01
期刊：
影响因子：
7.7
通讯作者：
Polychronakos, Constantin
中科院分区：
文献类型：
--
作者：
Li, Meihang;Wang, Sihua;Polychronakos, Constantin
据估计，临床诊断为1型糖尿病（T1D）的欧洲血统患者中约有1%实际上患有该疾病的单基因形式。由于东亚人真正的T1D发病率要低得多，我们假设这个百分比会高得多。为了验证这一点，我们对82名临床诊断为T1D但三种自身抗体阴性的中国汉族患者的外显子组进行了测序。分析集中在已建立或提出的单基因糖尿病基因。我们在82例自身抗体阴性患者中的18例（22%）中发现了可信的突变。所有的突变都有共识的致病性支持的五个算法。与欧洲人一样，最常见的基因是HNF1A（MODY3），18例中有6例。令人惊讶的是，WFS1的双等位基因突变几乎同样频繁，已知会导致Wolfram综合征，但也在非综合征病例中描述。空腹C肽变化很大，没有预测性。考虑到中国人27.4%的自身抗体阴性和22%的突变率，我们估计大约6%的临床诊断为T1D的中国人患有单基因糖尿病。我们的研究结果支持将自身抗体阴性病例的通用测序作为东亚临床T1D诊断患者的标准治疗。WSF 1基因突变的非综合征型糖尿病在中国并不罕见。应调查其对替代治疗的反应。
It is estimated that similar to 1% of European ancestry patients clinically diagnosed with type 1 diabetes (T1D) actually have monogenic forms of the disease. Because of the much lower incidence of true T1D in East Asians, we hypothesized that the percentage would be much higher. To test this, we sequenced the exome of 82 Chinese Han patients clinically diagnosed with T1D but negative for three autoantibodies. Analysis focused on established or proposed monogenic diabetes genes. We found credible mutations in 18 of the 82 autoantibody-negative patients (22%). All mutations had consensus pathogenicity support by five algorithms. As in Europeans, the most common gene was HNF1A (MODY3), in 6 of 18 cases. Surprisingly, almost as frequent were diallelic mutations in WFS1, known to cause Wolfram syndrome but also described in nonsyndromic cases. Fasting C-peptide varied widely and was not predictive. Given the 27.4% autoantibody negativity in Chinese and 22% mutation rate, we estimate that similar to 6% of Chinese with a clinical T1D diagnosis have monogenic diabetes. Our findings support universal sequencing of autoantibody-negative cases as standard of care in East Asian patients with a clinical T1D diagnosis. Nonsyndromic diabetes with WSF1 mutations is not rare in Chinese. Its response to alternative treatments should be investigated.