title: Wolfram/DIDMOAD syndrome, a heterogenic and molecularly complex neurodegenerative disease.
abstract: Wolfram syndrome (WS, OMIM 22233), is a rare, autosomal recessive, and neurodegenerative disease. The syndrome is also known as DIDMOAD, the acronym for diabetes insipidus diabetes mellitus, optic atrophy and deafness, which summarizes the main clinical features, among many others, in WS patients. The gene associated with the syndrome, called WFS1, is located in the 4p16.1 region. The WFS1 gene encodes for a transmembrane protein located in the endoplasmic reticulum. Although the function of the WFS1 protein remains unknown, it is thought to be related with intracellular calcium homeostasis. The pattern of presentation of WS suggested the existence of mitochondrial impairment. Mitochondrial DNA rearrangements were detected in some patients, thus confirming that hypothesis. Recently, a particular WS phenotype has been described linked with the long arm of chromosome 4. This work aims to summarize the current knowledge about this disease that causes a heterogeneous phenotype and has a complex molecular aetiology.
authors.affiliation: Centre de Genetica Medica i Molecular-Institut de Recerca Oncologica (CGMM-IRO)-IDIBELL, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Domenech
authors.forename: Montse
authors.initials: M
authors.lastname: Gomez-Zaera
authors.forename: Virginia
authors.initials: V
authors.lastname: Nunes
mesh_terms: D000293:Adolescent; D002118:Calcium / Q000378:metabolism; D002648:Child; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000737:chemistry; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D009154:Mutation; D010641:Phenotype; D014929:Wolfram Syndrome / Q000175:diagnosis / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D008565:Membrane Proteins; C114987:wolframin protein; D002118:Calcium