Endocrine Abstracts

Congenital hypoglycemic hyperinsulinemia (CHI) is a clinical and genetic heterogeneous entity. Clinical manifestations can vary from serious life threatening to milder difficultly identifiable cases. Children who don’t react adequate to medical treatment are subject to pancreatic recession. The molecular ethiology are from recessive mutations of the ABCC8 (SUR1) and KCNJ11 (Kir6.2) to dominant mutations of the GCK or GDH genes. Focal dysplasia characterised by loos of maternal Chromosome 11 and hereby ABCC8 and KCNJ11 is a common cause of CHI. In some studies mutations in the ABCC8 promotor have been shown to cause CHI. In approximately 50% of the incidences the disease is still genetically unexplained necessitating the search for other genetic factors.

The purpose of the present study was to identify new genetic causes of CHI in patients with a hitherto unexplained manifestation.

46 children and there parents was tested for mutations in the ABCC8 and KCNJ11 promotors by D-HPLC and sequencing. Samples with deviating chromatographic patterns were sequenced.

The a region covering 1063 bp including the minimal KCNJ11 promoter and a region covering 930 pb including the ABCC8 minimal promoter was analysed. In 13 samples a c.-507 del T mutation was found in the KCNJ11 gene. This variant has not previously been described. Using SIGSCAN and TRANSFAC software possible transcription factor binding sites was predicted in this region site. No other variants were found in either of the two genes. If the c.-507 delT variant is a common cause of CHI in Denmark has to be further investigated.