Prevalence and Clinical Characteristics of PDX1 Variant Induced Diabetes in Chinese Early-Onset Type 2 Diabetes

Context: Maturity-onset diabetes of the young 4 (MODY4) is caused by mutations of PDX1; its prevalence and clinical features are not well known.

Objective: This study aimed to investigate the prevalence and clinical characteristics of MODY4 in Chinese people clinically diagnosed with early-onset type 2 diabetes (EOD), and to evaluate the relationship between the PDX1 genotype and the clinical phenotype.

Method: The study cohort consisted of 679 patients with EOD. PDX1 mutations were screened by DNA sequencing, and their pathogenicity was evaluated by functional experiments and American College of Medical Genetics and Genomics guidelines. MODY4 was diagnosed in individuals with diabetes who carry a pathogenic or likely pathogenic PDX1 variant. All reported cases were reviewed for analyzing the genotype-phenotype relationship.

Result: 4 patients with MODY4 were identified, representing 0.59% of this Chinese EOD cohort. All the patients were diagnosed before 35 years old, either obese or not obese. Combined with previously reported cases, the analysis revealed that the carriers of homeodomain variants were diagnosed earlier than those with transactivation domain variants (26.10 ± 11.00 vs 41.85 ± 14.66 years old, P < .001), and the proportions of overweight and obese individuals with missense mutation were higher than those with nonsense or frameshift mutations (27/34 [79.4%] vs 3/8 [37.5%], P = .031).

Conclusion: Our study suggested that MODY4 was prevalent in 0.59% of patients with EOD in a Chinese population. It was more difficult to identify clinically than other MODY subtypes owning to its clinical similarity to EOD. Also, this study revealed that there is some relationship between genotype and phenotype.