NEUROD1-deficient diabetes (MODY6): Identification of the first cases in Japanese and the clinical features

作者：Horikawa Yukio^*; Enya Mayumi; Mabe Hiroyo; Fukushima Kei; Takubo Noriyuki; Ohashi Masaaki; Ikeda Fuki; Hashimoto Ken ichi; Watada Hirotaka; Takeda Jun

来源：Pediatric Diabetes, 2018, 19(2): 236-242.

DOI：10.1111/pedi.12553

• beta cell dysfunction
• ketosis
• low penetrance
• MODY
• neurological abnormality

Aims: Only a few families with neuronal differentiation 1 (NEUROD1)-deficient diabetes, currently designated as maturity-onset diabetes of the young 6 (MODY6), have been reported, but mostly in Caucasian, and no mutation has been identified by family-based screening in Japanese. Accordingly, the phenotypic details of the disease remain to be elucidated.
Methods: We examined a total of 275 subjects having diabetes suspected to be MODY who were negative for mutations in MODY1-5 referred from 155 medical institutions throughout Japan. So as not to miss low penetrant cases, we examined non-obese Japanese patients with early-onset diabetes regardless of the presence of family history by direct sequencing of all exons and flanking regions of NEUROD1. Large genomic rearrangements also were examined.
Results: Four patients with 3 frameshift mutations and 1 missense mutation, all of which were heterozygous and 3 of which were novel, were identified. Diabetic ketosis was found occasionally in these patients even under conditions of chronic hyperglycemia, for unknown reasons. Although the capacity of early-phase insulin secretion was low in these patients, the insulin secretory capacity was relatively preserved compared to that in hepatocyte nuclear factor (HNF) 1A- and HNF1B-MODY. One of the patients and 2 of their diabetic mothers were found to have some mental or neuronal abnormality.
Conclusions: This is the first report of NEUROD1 mutations in Japanese, who have a genetic background of intrinsically lower capacity of insulin secretion. NEUROD1-deficient diabetes appears to be low penetrant, and may occur in concert with other genetic factors.

• 出版日期2018-3