title: Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro).
abstract: Wolfram syndrome, also named "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an inherited association of juvenile-onset diabetes mellitus and optic atrophy as key diagnostic criteria. Renal tract abnormalities and neurodegenerative disorder may occur in the third and fourth decade. The wolframin gene, WFS1, associated with this syndrome, is located on chromosome 4p16.1. Many mutations have been described since the identification of WFS1 as the cause of Wolfram syndrome. We identified a new homozygous WFS1 mutation (c.1532T>C; p.Leu511Pro) causing Wolfram syndrome in a large inbred Turkish family. The patients showed early onset of IDDM, diabetes insipidus, optic atrophy, sensorineural hearing impairment and very rapid progression to renal failure before age 12 in three females. Ectopic expression of the wolframin mutant in HEK cells results in greatly reduced levels of protein expression compared to wild-type wolframin, strongly supporting that this mutation is disease-causing. The mutation showed perfect segregation with disease in the family, characterized by early and severe clinical manifestations.
authors.affiliation: Yuzuncu Yil University, School of Medicine, Department of Pediatric Endocrinology, Van, Turkey. sevilyuca@yahoo.com
authors.forename: Sevil Ari
authors.initials: SA
authors.lastname: Yuca
authors.forename: Nanna Dahl
authors.initials: ND
authors.lastname: Rendtorff
authors.forename: Houda
authors.initials: H
authors.lastname: Boulahbel
authors.forename: Marianne
authors.initials: M
authors.lastname: Lodahl
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Tranebjærg
authors.forename: Yasar
authors.initials: Y
authors.lastname: Cesur
authors.forename: Murat
authors.initials: M
authors.lastname: Dogan
authors.forename: Cahide
authors.initials: C
authors.lastname: Yilmaz
authors.forename: Cihangir
authors.initials: C
authors.lastname: Akgun
authors.forename: Mehmet
authors.initials: M
authors.lastname: Acikgoz
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics / Q000378:metabolism; D003241:Consanguinity; D005260:Female; D057809:HEK293 Cells; D006720:Homozygote; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D014421:Turkey / Q000453:epidemiology; D014929:Wolfram Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein