Congenital sucrase–isomaltase deficiency: identification of a common Inuit founder mutation
| Autor: | Kheirie Issa, Margaret Boland, Michael T. Geraghty, C. Ronald Scott, Zaining Wu, Adam D. McIntyre, Robert A. Hegele, Matthew A. Lines, Julien L. Marcadier |
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| Rok vydání: | 2014 |
| Předmět: |
Proband
medicine.medical_specialty Pediatrics Malabsorption Research General Medicine Biology Congenital Sucrase-Isomaltase Deficiency medicine.disease Frameshift mutation Sucrase-isomaltase complex Endocrinology Internal medicine Failure to thrive medicine medicine.symptom Allele frequency Founder effect |
| Zdroj: | Canadian Medical Association Journal. 187:102-107 |
| ISSN: | 1488-2329 0820-3946 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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