Increased Prevalence of Rare Sucrase-isomaltase Pathogenic Variants in Irritable Bowel Syndrome Patients

Koldo Garcia-Etxebarria, Tenghao Zheng, Ferdinando Bonfiglio, Luis Bujanda, Aldona Dlugosz, Greger Lindberg, Peter T. Schmidt, Pontus Karling, Bodil Ohlsson, Magnus Simren, Susanna Walter, Gerardo Nardone, Rosario Cuomo, Paolo Usai-Satta, Francesca Galeazzi, Matteo Neri, Piero Portincasa, Massimo Bellini, Giovanni Barbara, Daisy JonkersShanti Eswaran, William D. Chey, Purna Kashyap, Lin Chang, Emeran A. Mayer, Mira M. Wouters, Guy Boeckxstaens, Michael Camilleri, Andre Franke, Mauro D'Amato

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59 Citations (Scopus)


Patients with irritable bowel syndrome (IBS) often associate their symptoms to certain foods. In congenital sucrase-isomaltase deficiency (CSID), recessive mutations in the SI gene (coding for the disaccharidase digesting sucrose and 60% of dietary starch)1 cause clinical features of IBS through colonic accumulation of undigested carbohydrates, triggering bowel symptoms.2 Hence, in a previous study,3 we hypothesized that CSID variants reducing SI enzymatic activity may contribute to development of IBS symptoms. We detected association with increased risk of IBS for 4 rare loss-of-function variants typically found in (homozygous) CSID patients, because carriers (heterozygous) of these rare variants were more common in patients than in controls.1,4 Through a 2-step computational and experimental strategy, the present study aimed to determine whether other (dys-)functional SI variants are associated with risk of IBS in addition to known CSID mutations. We first aimed to identify all SI rare pathogenic variants (SI-RPVs) on the basis of integrated Mendelian Clinically Applicable Pathogenicity (M-CAP) and Combined Annotation Dependent Depletion (CADD) predictive (clinically relevant) scores; next, we inspected genotype data currently available for 2207 IBS patients from a large ongoing project to compare SI-RPV case frequencies with ethnically matched population frequencies from the Exome Aggregation Consortium (ExAC).

Original languageEnglish
Pages (from-to)1673-1676
Number of pages4
JournalClinical Gastroenterology and Hepatology
Issue number10
Publication statusPublished - 1 Oct 2018
Externally publishedYes

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