Confirmation of a Rare Carbohydrate Metabolic Disorder through Next Generation Sequencing Technology

Abstract

Fanconi Bickel.Syndrome is a rare carbohydrate metabolic disease which is characterized by hepatomegaly, fasting hypglycemia, excessive proximal tubular dysfunction, rickets, growth retardation and excessive urination (polyuria). Fanconi Bickel.Syndrome is also termed as glycogen storage.disorder type XI. Abnormal glycogen aggregation in the liver and kidneys, which affects the body use of galactose and glucose and results in proximal renal tubular failure, is the first cause of FBS. The disease is .caused by the mutation in the SLC2A2 gene, which is located on chromosome 3 and contains total 11 exon. The candidate gene encodes for the facultative glucose transporter 2 (GLUT2) and its pattern of inheritance is an autosomal recessive. The encoded protein facilitates glucose transport in both directions and has been known for glucose sensor. The encoded gene is mainly expresses in the liver and kidney. The aim of our study was to diagnose the disorder having an autosomal recessive pattern. Whole exome sequencing .was performed to analyze the genomic DNA of the affected individual having disease causing pathogenic mutation. The exome data were then analyzed and different filters were used to find out the variant which are responsible for the disorder. A novel variant c.298T>C (p. Ser100Pro) was detected in the SLC2A2 gene of the proband in our targeted family. The different insilico tools were applied on the detected variant and these showed that the variant might be pathogenic and likely disease causing, so it might be the exact cause of the metabolic disorder. Moreover, protein expression studies are further recommended to better recognize the expression, structure and functional aspects of the novel variant. This proband family will be counseled on the basis of this result and the instruction will be provided to them for future planning. Furthermore, our study will expand the understanding of mutation spectrum and etiology of this disorder