Congenital sucrase-isomaltase deficiency: identification of a common Inuit founder mutation.
CMAJ
; 187(2): 102-107, 2015 Feb 03.
Article
em En
| MEDLINE
| ID: mdl-25452324
ABSTRACT
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Complexo Sacarase-Isomaltase
/
Erros Inatos do Metabolismo dos Carboidratos
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Inuíte
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Efeito Fundador
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Mutação
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Newborn
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article