RT Journal Article
SR Electronic
T1 Congenital sucrase–isomaltase deficiency: identification of a common Inuit founder mutation
JF Canadian Medical Association Journal
JO CMAJ
FD Canadian Medical Association
SP 102
OP 107
DO 10.1503/cmaj.140657
VO 187
IS 2
A1 Julien L. Marcadier
A1 Margaret Boland
A1 C. Ronald Scott
A1 Kheirie Issa
A1 Zaining Wu
A1 Adam D. McIntyre
A1 Robert A. Hegele
A1 Michael T. Geraghty
A1 Matthew A. Lines
YR 2015
UL http://www.cmaj.ca/content/187/2/102.abstract
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