The ABCC8 gene located on chromosome 11p15.1, gives instructions for making a protein called sulfonylurea receptor 1 (SUR1) protein.The SUR1 protein is a member of the ATP-binding cassette (ABC) transporters superfamily and the MRP subfamily.It is a subunit of the ATP-sensitive potassium (K-ATP) channel that is found across cell membranes in the beta cells of the pancreas.This protein functions as a regulator of ATP-sensitive K(+) channels and insulin release. Defects in this protein have been associated with leucine-induced hypoglycemia, familial hyperinsulinemic hypoglycemia 1, diabetes mellitus, permanent neonatal, and transient neonatal diabetes mellitus 2.
The ABCC8 gene has 39 coding exons spanning approximately84 kb, with alternatively spliced variants. At least 300 mutations in the ABCC8 gene have been identifiedin patients with congenital hyperinsulinism, and more than 14 mutations have been found to cause permanent neonatal diabetes mellitus. Mutations have also been associated with transient neonatal diabetes mellitus and an increased risk of type 2 diabetes mellitus.
See: [Saudi Arabia>Al Mutair et al., (2013)]
Al Mutair et al. (2013) described 15 patients from eight unrelated consanguineous families from Saudi Arabia and Kuwait with congenital hyperinsulinism and deafness. They analyzed the USH1C, ABCC8, and KCNJ11 genes by direct sequencing, multiplex ligation-dependent probe amplification, and microsatellite markers for the 15 patients. A homozygous a 122.815-base pair deletion of USH1C exon 3–28 and ABCC8 exon 1–22, USH1C:c.(90+592)_ABCC8: c.(2694–528)del was found in all 10 patients with available DNA, and in the parents it was heterozygous.
Deeb et al. (2016) examined Neonatal Diabetes Mellitus (NDM) patients and characterized their genetic and clinical features. The authors found 25 cases of NDM in Abu Dhabi between the years 1985-2013, giving an incidence rate of 1:29,241 live births. Of these, 23 were Permanent Neonatal Diabetes Mellitus (PNDM) cases and 2 patients had Transient Neonatal Diabetes Mellitus (TNDM). Genetic analysis of this cohort identified a heterozygous H410Y ABCC8 variant in a 15-year-old male patient. The affected individual was born full term with a birth weight of 2.4 kg to a non-consanguineous family. He was diagnosed with NDM at 25 weeks. At 15 years of age he had normal growth and intelligence and was on insulin pump therapy of 1.3U/kg/day. His 45-year-old mother was a carrier for the variant and had glucose intolerance with HbA1c of 5.9% on diet control.
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