PT  - JOURNAL ARTICLE
AU  - Julien L. Marcadier
AU  - Margaret Boland
AU  - C. Ronald Scott
AU  - Kheirie Issa
AU  - Zaining Wu
AU  - Adam D. McIntyre
AU  - Robert A. Hegele
AU  - Michael T. Geraghty
AU  - Matthew A. Lines
TI  - Congenital sucrase–isomaltase deficiency: identification of a common Inuit founder mutation
AID  - 10.1503/cmaj.140657
DP  - 2015 Feb 03
TA  - Canadian Medical Association Journal
PG  - 102--107
VI  - 187
IP  - 2
4099  - http://www.cmaj.ca/content/187/2/102.short
4100  - http://www.cmaj.ca/content/187/2/102.full
SO  - CMAJ2015 Feb 03; 187
AB  - Background: Congenital sucrase–isomaltase deficiency is a rare hereditary cause of chronic diarrhea in children. People with this condition lack the intestinal brush-border enzyme required for digestion of di- and oligosaccharides, including sucrose and isomaltose, leading to malabsorption. Although the condition is known to be highly prevalent (about 5%–10%) in several Inuit populations, the genetic basis for this has not been described. We sought to identify a common mutation for congenital sucrase–isomaltase deficiency in the Inuit population.Methods: We sequenced the sucrase–isomaltase gene, SI, in a single Inuit proband with congenital sucrase–isomaltase deficiency who had severe fermentative diarrhea and failure to thrive. We then genotyped a further 128 anonymized Inuit controls from a variety of locales in the Canadian Arctic to assess for a possible founder effect.Results: In the proband, we identified a novel, homozygous frameshift mutation, c.273_274delAG (p.Gly92Leufs*8), predicted to result in complete absence of a functional protein product. This change was very common among the Inuit controls, with an observed allele frequency of 17.2% (95% confidence interval [CI] 12.6%–21.8%). The predicted Hardy–Weinberg prevalence of congenital sucrase–isomaltase deficiency in Inuit people, based on this single founder allele, is 3.0% (95% CI 1.4%–4.5%), which is comparable with previous estimates.Interpretation: We found a common mutation, SI c.273_274delAG, to be responsible for the high prevalence of congenital sucrase–isomaltase deficiency among Inuit people. Targeted mutation testing for this allele should afford a simple and minimally invasive means of diagnosing this condition in Inuit patients with chronic diarrhea.See also research article on page E68 and at www.cmaj.ca/lookup/doi/10.1503/cmaj.140840 and commentary on page 93 and at www.cmaj.ca/lookup/doi/10.1503/cmaj.141509