Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University) Ministry of Education, Sichuan University, Chengdu, China.
Front Endocrinol (Lausanne). 2023 Jan 6;13:1086785. doi: 10.3389/fendo.2022.1086785. eCollection 2022.
Neonatal diabetes mellitus (NDM) is a rare form of diabetes. We analyzed a novel insulin gene () mutation of a Chinese permanent neonatal diabetes mellitus (PNDM) patient to explore the clinical and genetic characteristics and put forward some opinions on treatment and its long-term management.
A proband was recruited who was diagnosed with permanent neonatal diabetes on his first day after birth. His clinical and follow-up data were collected for 10 years. All of the family members were given an oral glucose tolerance test. Whole exome sequencing was performed on the proband, and the genomic DNA of family members was used for verification by first-generation Sanger sequencing technology. The pathogenic variant was screened according to the American College of Medical Genetics and Genomics classification guidelines and the clinical phenotype of the patient.
The proband was diagnosed on the first day after birth, presenting with low birth weight, progressive hyperglycemia, and insulin deficiency. His parents and grandfathers were confirmed to have normal blood sugar levels. A novel homozygous mutation of c.1T>C in the gene was detected in the proband, located in the initiation codon. The heterozygous mutations were found in four family members, including his mother, father, and grandfathers. With regular insulin injections, long-term regular follow-up, close monitoring of blood glucose, balanced exercise and diet, and psychological and mutual family support, the blood glucose level was well controlled; there were no acute or chronic complications during this decade. The patient's growth and nervous system development are now no different to those of the same age.
A favorable prognosis is presented for a permanent neonatal diabetes mellitus (PNDM) patient with a novel mutation in the gene in China. The present findings indicate that the genetic diagnosis, early use of insulin, close monitoring of blood glucose, and psychological and mutual family support for patients with mutation are necessary for their favorable long-term prognosis.
新生儿糖尿病（NDM）是一种罕见的糖尿病形式。我们分析了一位中国永久性新生儿糖尿病（PNDM）患者的新型胰岛素基因突变，以探讨其临床和遗传特征，并就治疗及其长期管理提出一些意见。
我们招募了一位在出生后第一天被诊断为永久性新生儿糖尿病的先证者。收集了他 10 年的临床和随访数据。所有家庭成员均进行口服葡萄糖耐量试验。对先证者进行全外显子组测序，并用第一代 Sanger 测序技术对家系成员的基因组 DNA 进行验证。根据美国医学遗传学与基因组学学院分类指南和患者的临床表型筛选致病性变异。
先证者在出生后第 1 天被诊断为患有糖尿病，表现为出生体重低、进行性高血糖和胰岛素缺乏。他的父母和祖父被证实血糖水平正常。在先证者中检测到胰岛素基因 c.1T>C 中的新型纯合突变，位于起始密码子。在四个家庭成员中发现了杂合突变，包括他的母亲、父亲和祖父。通过定期注射胰岛素、长期定期随访、密切监测血糖、均衡的运动和饮食、心理和相互家庭支持，血糖得到了很好的控制；在这十年中没有出现急性或慢性并发症。患者的生长和神经系统发育现在与同龄儿童无异。
在中国，胰岛素基因新型突变导致的永久性新生儿糖尿病（PNDM）患者预后良好。本研究结果表明，对携带 基因突变的患者进行遗传诊断、早期使用胰岛素、密切监测血糖以及心理和相互家庭支持，对于其长期预后良好是必要的。
