Congenital Hyperinsulinism of Infancy (CHI) is a rare disorder, characterized by heterogeneity in clinical and genetic features. An inappropriate insulin secretion is responsible of hypoglycaemia, which can result in serious neurological damage and life-long handicap. The genetic causes of CHI have been found in genes regulating insulin secretion from pancreatic beta-cells but in about 50 % of CHI patients the molecular defect remain unknown. Hunting for novel CHI-causing genes we performed whole-exome sequencing (WES) on 10 CHI patients doi:10.1371/journal.pone.0068740]. To pinpoint the causal mutation in a small number of samples and to select the most promising candidate genes, we implemented a complex bioinformatics strategy including: 1) a bionformatics pipeline to identify a high quality single nucleotide variants (SNV); 2) an exome homozygosity mapping using a novel algorithm H3M2 at the level of single patient http://homes.esat.kuleuven.be/~bioiuser/gpp/index.php] and 3) a prioritization analysis strategy using the total list of rare and novel gene variants by mean of prioritization web tools such as ToppGene suite, Endeavour and Gene Distiller [doi: 10.1038/nrg3253.]. The results of prioritization analysis suggested a set of genes that significantly correlate with phenotypes associated to CHI. Among them we selected missense mutations affecting CDKAL1 and PIK3R1 for further investigations at the level of protein structure and respect to their role in beta cell function using INS-1E cellular model and human pancreatic islets.

Congenital Hyperinsulinism of Infancy (CHI) : hunt for new genes / C. Battaglia, C. Cosentino, M. Proverbio, A. Pietrelli, E. Mangano, R. Bordoni, C. Perego, E. Di Cairano, A. Maggi, L. Tattini, G. De Bellis. ((Intervento presentato al convegno European Human Genetics Conference tenutosi a Milano nel 2014.

Congenital Hyperinsulinism of Infancy (CHI) : hunt for new genes

C. Battaglia;C. Cosentino;M. Proverbio;A. Pietrelli;E. Mangano;R. Bordoni;C. Perego;E. Di Cairano;A. Maggi;
2014-05-31

Abstract

Congenital Hyperinsulinism of Infancy (CHI) is a rare disorder, characterized by heterogeneity in clinical and genetic features. An inappropriate insulin secretion is responsible of hypoglycaemia, which can result in serious neurological damage and life-long handicap. The genetic causes of CHI have been found in genes regulating insulin secretion from pancreatic beta-cells but in about 50 % of CHI patients the molecular defect remain unknown. Hunting for novel CHI-causing genes we performed whole-exome sequencing (WES) on 10 CHI patients doi:10.1371/journal.pone.0068740]. To pinpoint the causal mutation in a small number of samples and to select the most promising candidate genes, we implemented a complex bioinformatics strategy including: 1) a bionformatics pipeline to identify a high quality single nucleotide variants (SNV); 2) an exome homozygosity mapping using a novel algorithm H3M2 at the level of single patient http://homes.esat.kuleuven.be/~bioiuser/gpp/index.php] and 3) a prioritization analysis strategy using the total list of rare and novel gene variants by mean of prioritization web tools such as ToppGene suite, Endeavour and Gene Distiller [doi: 10.1038/nrg3253.]. The results of prioritization analysis suggested a set of genes that significantly correlate with phenotypes associated to CHI. Among them we selected missense mutations affecting CDKAL1 and PIK3R1 for further investigations at the level of protein structure and respect to their role in beta cell function using INS-1E cellular model and human pancreatic islets.
Congenital Hyperinsulinism of Infancy
Settore BIO/09 - Fisiologia
Settore BIO/18 - Genetica
Settore BIO/11 - Biologia Molecolare
Congenital Hyperinsulinism of Infancy (CHI) : hunt for new genes / C. Battaglia, C. Cosentino, M. Proverbio, A. Pietrelli, E. Mangano, R. Bordoni, C. Perego, E. Di Cairano, A. Maggi, L. Tattini, G. De Bellis. ((Intervento presentato al convegno European Human Genetics Conference tenutosi a Milano nel 2014.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/252489
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