Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong 226001, China.
J Mol Cell Biol. 2023 Nov 27;15(6). doi: 10.1093/jmcb/mjad040.
A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic cause. Here, we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesity or diabetes. We performed this panel in 481 patients to detect causative variants and compared these results with whole-exome sequencing (WES) data available for 146 of these patients. The coverage of targeted gene panel sequencing was significantly higher than that of WES. The diagnostic yield in patients sequenced by the panel was 32.9% with subsequent WES leading to three additional diagnoses with two novel genes. In total, 178 variants in 83 genes were detected in 146 patients by targeted sequencing. Three of the 178 variants were missed by WES, although the WES-only approach had a similar diagnostic yield. For the 335 samples only receiving targeted sequencing, the diagnostic yield was 32.2%. In conclusion, taking into account the lower costs, shorter turnaround time, and higher quality of data, targeted sequencing is a more effective screening method for monogenic obesity and diabetes compared to WES. Therefore, this approach could be routinely established and used as a first-tier test in clinical practice for specific patients.
一小部分被诊断为肥胖症或糖尿病的患者存在潜在的单基因病因。在这里，我们构建了一个靶向基因panel，其中包含了 83 个被报道与单基因肥胖或糖尿病有关的基因。我们对 481 名患者进行了panel 检测，以发现致病变异，并将这些结果与 146 名患者的全外显子组测序（WES）数据进行了比较。靶向基因 panel 测序的覆盖度明显高于 WES。通过 panel 测序的患者的诊断率为 32.9%，随后的 WES 又导致了另外三个诊断结果，涉及两个新基因。总共，在 146 名患者中，通过靶向测序检测到 83 个基因中的 178 个变异。178 个变异中有 3 个被 WES 漏检，尽管 WES 方法的诊断率相似。对于仅接受靶向测序的 335 个样本，诊断率为 32.2%。总之，考虑到较低的成本、较短的周转时间和更高的数据质量，与 WES 相比，靶向测序是一种更有效的单基因肥胖和糖尿病筛查方法。因此，这种方法可以在临床上常规建立并作为特定患者的一线检测方法。
