) gene cause congenital chloride diarrhoea

来自 Nature

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作者：

Pia Hglund，S Haila，J Socha，L Tomaszewski，U Saarialho-Kere，ML Karjalainen-Lindsberg，K Airola，C Holmberg，ADL Chapelle，J Kere

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摘要：

A major transport function of the human intestine involves the absorption of chloride in exchange for bicarbonate. We have studied a recessively inherited defect of this exchange, congenital chloride diarrhoea (CLD; MIM 214700). The clinical presentation of CLD is a lifetime, potentially fatal diarrhoea with a high chloride content. Thelocus was previously mapped to 7q31 adjacent to the cystic fibrosis gene (). By refined genetic and physical mapping, a cloned gene having anion transport function, Down-regulated in adenoma (), was implicated as a positional and functional candidate for. In this study, we report segregation of two missense mutations, ΔV317 and H124L, and one frameshift mutation, 344delT, ofin 32 Finnish and four Polish CLD patients. The disease-causing nature of δV317 is supported by genetic data in relation to the population history of Finland. By mRNAhybridization, we demonstrate that the expression ofoccurs preferentially in highly differentiated colonic epithelial cells, is unchanged in Finnish CLD patients with ΔV317, and is low in undifferentiated (including neoplastic) cells. We conclude that DFIA is an intestinal anion transport molecule that causes chloride diarrhoea when mutated.

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关键词：

Humans Adenoma Colonic Neoplasms Chlorides Diarrhea Metabolism, Inborn Errors Membrane Proteins Antiporters Incidence Blotting, Northern