Cytogenetic location: 6p21.3 Genomic coordinates (GRCh38) : 6:30,500,001-36,600,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 6p21.3 | ?Diabetes mellitus, insulin-dependent, neonatal | 600089 | Autosomal recessive | 2 |
Blum et al. (1993) described a newborn with congenital absence of the insulin-producing beta cells from otherwise normal-appearing pancreatic islets, causing insulin-dependent diabetes mellitus. The infant also had methylmalonic acidemia (251000) and died 16 days after birth. By serotyping of the HLA antigens, DNA typing of HLA-B and HLA class II loci, and study of polymorphic DNA markers of chromosome 6, Abramowicz et al. (1994) demonstrated that the infant had paternal uniparental isodisomy involving at least a 25-cM portion of chromosome 6 that encompasses the MHC. The methylmalonic acidemia was easily explained by duplication of the mutant gene on chromosome 6 inherited from the carrier father. The agenesis of beta cells and consequent insulin-dependent diabetes mellitus suggested the existence of a gene on chromosome 6 involved in beta-cell differentiation. Permanent insulin-dependent diabetes mellitus is very rare in the neonatal period. Abramowicz et al. (1994) stated that 31 well-documented cases had been published (see Dorchy et al., 1974). In most, the pathogenesis is unknown. A very early presentation of autoimmune destruction, which is the most common cause of insulin-dependent diabetes mellitus, had never been irrefutably demonstrated. Rare causes such as aplasia of the pancreas (260370, 600001) and absence of the islets of Langerhans (304790) had been reported. Abramowicz et al. (1994) stated that isolated absence of the beta cells had been shown in one case. Presumably, the disorder is an autosomal recessive.
Abramowicz, M. J., Andrien, M., Dupont, E., Dorchy, H., Parma, J., Duprez, L., Ledley, F. D., Courtens, W., Vamos, E. Isodisomy of chromosome 6 in a newborn with methylmalonic acidemia and agenesis of pancreatic beta cells causing diabetes mellitus. J. Clin. Invest. 94: 418-421, 1994. [PubMed: 7913714] [Full Text: https://doi.org/10.1172/JCI117339]
Blum, D., Dorchy, H., Mouraux, T., Vamos, E., Mardens, Y., Kumps, A., De Prez, C., Heimann, P., Fowler, B., Baumgartner, R., Bouwens, L., Van Gompel, J., Kloppel, G. Congenital absence of insulin cells in a neonate with diabetes mellitus and mutase-deficient methylmalonic acidaemia. Diabetologia 36: 352-357, 1993. Note: Erratum: Diabetologia 36: 1332 only, 1993. [PubMed: 8097481] [Full Text: https://doi.org/10.1007/BF00400240]
Dorchy, H., Ooms, H., Loeb, H. Permanent neonatal diabetes mellitus: a case report with plasma insulin studies. Z. Kinderheilk. 118: 271-281, 1974.