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 do not 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.
ABCC8 and KCNJ11 is localised to chromosome 11p15. Interestingly the USH1C gene is localised upstream of ABCC8. Usher syndrome type I caused by mutations in USH1C is an autosomal recessive sensory defect involving congenital profound sensorineural deafness, vestibular dysfunction, and blindness due to progressive retinitis pigmentosa.
The adjacent USH1c gene and ABCC8 gene of chromosome 11p15 were analysed using quantitative realtime PCR and microsatellite markers to analyse for Loss of heterozygosity (LOH), and sequencing.
The microsatellite D11S902 was absent. By PCR of ABCC8 it was shown that only exon 23* to 39 are present. All of KCNJ11 is present. In the same way only exon 1 and 2 of the USH1c gene was shown to be present. By sequencing, a homozygous contiguous partial gene deletion was identified, starting in USH1c intron 2, c.90+592, and ending in ABCC8 intron 21.
We here report the analysis of a patient with a complex phenotype that can be explained by a large deletion involving two genes.