ABCMdb

PMID: 15356046

Magge SN, Shyng SL, MacMullen C, Steinkrauss L, Ganguly A, Katz LE, Stanley CA
Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor.
J Clin Endocrinol Metab. 2004 Sep;89(9):4450-6., [PubMed]

Sentences

No. Mutations Sentence Comment

160 ABCC8 p.Glu1506Lys There have been two previous descriptions of dominantly inherited SUR1 mutations, E1506K by Huopio et al. (15) and delSer1387 from our institution (16). Login to comment 161 ABCC8 p.Glu1506Lys The E1506K mutation caused HI in seven children within a large pedigree. Login to comment 165 ABCC8 p.Glu1506Lys Unlike the R1353H and E1506K families, the delSer1387 family members showed only partial diazoxide responsiveness (16). Login to comment 168 ABCC8 p.Glu1506Lys In patch-clamp expression studies, E1506K SUR1 formed KATP channels that were sensitive to diazoxide, but not to metabolic inhibition, consistent with partial impairment of function (15). Login to comment 172 ABCC8 p.Glu1506Lys Thus, the R1353H mutation appears to cause a partial disruption of SUR1 receptor function similar to E1506K, but less severe than delSer1387. Login to comment 173 ABCC8 p.Glu1506Lys The milder impairment of function by R1353H and E1506K compared with delSer1387 correlates with the greater diazoxide responsiveness of patients with these two mutations. Login to comment 220 ABCC8 p.Glu1506Lys This was also noted in the family with the dominant E1506K SUR1 mutation described by Huopio et al. (15). Login to comment 222 ABCC8 p.Glu1506Lys Based on their observations of subnormal insulin responses to oral and iv glucose and to hyperglycemic clamp studies in adults with the SUR1 E1506K mutations, Huopio et al. (15) suggested that the KATP defect causes diabetes due to beta-cell apoptosis as a result of continuous depolarization and high cytoplasmic calcium concentrations of beta-cells. Login to comment 223 ABCC8 p.Glu1506Lys Supporting this hypothesis is their finding that insulin secretion was lower in older compared with younger E1506K heterozygotes (23). Login to comment