Department of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Center. No. 11, Beijing 100044, China.
Department of Endocrinology, Beijing Airport Hospital. No. 49, Beijing 101318, China.
J Clin Endocrinol Metab. 2023 Nov 17;108(12):e1686-e1694. doi: 10.1210/clinem/dgad303.
Maturity-onset diabetes of the young 4 (MODY4) is caused by mutations of PDX1; its prevalence and clinical features are not well known.
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.
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.
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).
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.
青年起病的成年型糖尿病 4 型（MODY4）由 PDX1 突变引起；其流行率和临床特征尚不清楚。
本研究旨在调查临床上诊断为早发 2 型糖尿病（EOD）的中国人中 MODY4 的流行率和临床特征，并评估 PDX1 基因型与临床表型之间的关系。
研究队列由 679 名 EOD 患者组成。通过 DNA 测序筛选 PDX1 突变，并通过功能实验和美国医学遗传学与基因组学学院指南评估其致病性。在携带致病性或可能致病性 PDX1 变异的糖尿病患者中诊断为 MODY4。对所有报告的病例进行回顾性分析，以探讨基因型-表型关系。
鉴定出 4 例 MODY4 患者，占该中国 EOD 队列的 0.59%。所有患者均在 35 岁之前被诊断出患有糖尿病，或肥胖或不肥胖。结合之前报道的病例，分析表明同源域变异携带者的诊断年龄早于转录激活域变异携带者（26.10±11.00 岁 vs 41.85±14.66 岁，P<0.001），错义突变的超重和肥胖个体比例高于无义或移码突变（27/34 [79.4%] 比 3/8 [37.5%]，P=0.031）。
本研究表明，MODY4 在中国人 EOD 患者中的患病率为 0.59%。由于其与 EOD 的临床相似性，临床上比其他 MODY 亚型更难识别。此外，本研究还揭示了基因型和表型之间存在一定的关系。
