1. Molecular Basis of Neonatal Diabetes in Japanese Patients
- Author
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Kenji Fujieda, Kumihiro Matsuo, Yoshio Makita, Osamu Ueda, Tokuo Mukai, and Shigeru Suzuki
- Subjects
Male ,旭川医科大学：博士（医学）（甲第384号） ,Potassium Channels ,Endocrinology, Diabetes and Metabolism ,Developmental Disabilities ,Receptors, Drug ,Clinical Biochemistry ,medicine.disease_cause ,Sulfonylurea Receptors ,Biochemistry ,Infant, Newborn, Diseases ,学位授与年月日：平成20年3月25日 ,Endocrinology ,Neonatal diabetes mellitus ,Macroglossia ,Prevalence ,Birth Weight ,Enteropathy ,X-linked recessive inheritance ,biology ,Forkhead Transcription Factors ,Chromosomes, Human, Pair 6 ,Female ,medicine.medical_specialty ,Context (language use) ,ABCC8 ,Asian People ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Genetic Predisposition to Disease ,Potassium Channels, Inwardly Rectifying ,Homeodomain Proteins ,Epilepsy ,Genetic heterogeneity ,business.industry ,Biochemistry (medical) ,Infant, Newborn ,Infant ,Recovery of Function ,Immune dysregulation ,medicine.disease ,Diabetes Mellitus, Type 1 ,Mutation ,biology.protein ,Trans-Activators ,ATP-Binding Cassette Transporters ,business - Abstract
Context: Neonatal diabetes mellitus (NDM) is classified clinically into a transient form (TNDM), in which insulin secretion recovers within several months, and a permanent form (PNDM), requiring lifelong medication. However, these conditions are genetically heterogeneous. Objective: Our objective was to evaluate the contribution of the responsible gene and delineate their clinical characteristics. Patients and Methods: The chromosome 6q24 abnormality and KCNJ11 and ABCC8 mutations were analyzed in 31 Japanese patients (16 with TNDM and 15 with PNDM). Moreover, FOXP3 and IPF1 mutations were analyzed in a patient with immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome and with pancreatic agenesis, respectively. Results: A molecular basis for NDM was found in 23 patients: 6q24 in eleven, KCNJ11 in nine, ABCC8 in two, and FOXP3 in one. All the patients with the 6q24 abnormality and two patients with the KCNJ11 mutation proved to be TNDM. Five mutations were novel: two (p.A174G and p.C166Y) in KCNJ11, two (p.A90V and p.N1122D) in ABCC8, and one (p.P367L) in FOXP3. Comparing the 6q24 abnormality and KCNJ11 mutation, there were some significant clinical differences: the earlier onset of diabetes, the lower frequency of diabetic ketoacidosis at onset, and the higher proportion of the patients with macroglossia at initial presentation in the patients with 6q24 abnormality. In contrast, two patients with the KCNJ11 mutations manifested epilepsy and developmental delay. Conclusions: Both the 6q24 abnormality and KCNJ11 mutation are major causes of NDM in Japanese patients. Clinical differences between them could provide important insight into the decision of which gene to analyze in affected patients first.