Identification of novel pathogenic variants in genes related to pancreatic β cell function: A multi-center study in Chinese with young-onset diabetes

Abstract

[4] Since the majority of previous studies on monogenic diabetes have primarily focused on populations of European descent, particularly in pediatric groups, a lack of comprehensive understanding of the clinical and genetic architecture of MODY in Chinese patients constrains the development of relevant genetic services within the health care system. [...]in this multi-center study, we aimed to identify novel pathogenic variants in MODY genes in three cohorts from three centers, and thereby obtain essential information for effective implementation of risk assessment, genetic counseling, and personalized therapies for those with MODY in China. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, 24 rare variants were categorized as pathogenic (P). According to the final variant classification, 25 P and 13 LP were identified in 56 patients, and defined as “Positive cases (N = 38)”, achieving a diagnostic rate of 18.5% (38/205) [Supplementary Figure 3A, http://links.lww.com/CM9/C343]. Additionally, 18 patients with VUS were defined as “VUS cases (N = 18)”, and the remaining 149 patients with no rare variants were defined as “Negative cases (N = 149)”. [...]seven patients had rare variants in two different MODY genes (KCNJ11 and FOXA2, HNF1A and ABCC8, GCK and INS, HNF4A and RFX6, APPL1 and RFX6, NEUROD1 and BLK, ABCC8 and ONECUT1) [Supplementary Table 4, http://links.lww.com/CM9/C343]. According to the ACMG guidelines, 10 rare variants were categorized as P, three as LP, and six as VUS [Supplementary Figure 3B and Supplementary Table 9, http://links.lww.com/CM9/C343].