SNOMEDCT: 609580007; ORPHA: 99886; DO: 0060334;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11p15.1 | Diabetes mellitus, transient neonatal 2 | 610374 | Autosomal dominant | 3 | ABCC8 | 600509 |
A number sign (#) is used with this entry because of evidence that transient neonatal diabetes mellitus-2 (TNDM2) is caused by heterozygous mutation in the ABCC8 gene (600509) on chromosome 11p15.
For a phenotypic description and a discussion of genetic heterogeneity of transient neonatal diabetes mellitus, see 601410.
From a group of 73 patients with neonatal diabetes, Babenko et al. (2006) screened the ABCC8 gene in 34 who did not have alterations in chromosome 6q (see 601410) or mutations in the KCNJ11 (600937) or GCK (138079) genes. They identified heterozygosity for 5 different mutations (see, e.g., 600509.0019 and 600509.0020) in 7 patients with transient neonatal diabetes mellitus. They also identified heterozygosity for mutations (600509.0017 and 600509.0018) in 2 patients with permanent neonatal diabetes (PNDM3; 618857). Mutant channels in intact cells and in physiologic concentrations of magnesium ATP had markedly higher activity than did wildtype channels. These overactive channels remained sensitive to sulfonylurea, and treatment with sulfonylureas resulted in euglycemia. The mutation-positive fathers of 5 of the probands with TNDM developed type II diabetes mellitus (125853) in adulthood; Babenko et al. (2006) proposed that mutations of the ABCC8 gene may give rise to a monogenic form of type II diabetes with variable expression and age at onset. The authors noted that dominant mutations in ABCC8 accounted for 12% of cases of neonatal diabetes in the study group.
Babenko, A. P., Polak, M., Cave, H., Busiah, K., Czernichow, P., Scharfmann, R., Bryan, J., Aguilar-Bryan, L., Vaxillaire, M., Froguel, P. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. New Eng. J. Med. 355: 456-466, 2006. [PubMed: 16885549] [Full Text: https://doi.org/10.1056/NEJMoa055068]