Wolfram syndrome （WFS; MIM 222300） is an autosomal recessive disorder with highly variable clinical manifestations. It is characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness （thus, k...Wolfram syndrome （WFS; MIM 222300） is an autosomal recessive disorder with highly variable clinical manifestations. It is characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness （thus, known as DIDMOAD syndrome） [ 1 ]. Other neurological and endocrine manifestations include dementia, psychiatric illnesses, renal-tract abnormalities, and bladder atony [2]. Gene linkage and positional cloning analysis reveal that a subset of Wolfram syndrome patients belonging to the WFS 1 group （MIM 606201） carry a loss-of-function mutation in the WFS1 gene, which encodes a transmembrane protein, Wolframin, localizing in the endoplasmic reticulm （ER） [3, 4]. Wolframin is thought to be involved in the regulation of ER stress and calcium ho- meostasis, and Wolframin deficiency in mice leads to progressive loss of β cells and impaired glucose tolerance, which is presumably caused by increased ER stress and apoptosis in the β cells.展开更多
文摘Wolfram syndrome （WFS; MIM 222300） is an autosomal recessive disorder with highly variable clinical manifestations. It is characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness （thus, known as DIDMOAD syndrome） [ 1 ]. Other neurological and endocrine manifestations include dementia, psychiatric illnesses, renal-tract abnormalities, and bladder atony [2]. Gene linkage and positional cloning analysis reveal that a subset of Wolfram syndrome patients belonging to the WFS 1 group （MIM 606201） carry a loss-of-function mutation in the WFS1 gene, which encodes a transmembrane protein, Wolframin, localizing in the endoplasmic reticulm （ER） [3, 4]. Wolframin is thought to be involved in the regulation of ER stress and calcium ho- meostasis, and Wolframin deficiency in mice leads to progressive loss of β cells and impaired glucose tolerance, which is presumably caused by increased ER stress and apoptosis in the β cells.
