Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro)

TY - JOUR

T1 - Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro)

AU - Yuca, Sevil Ari

AU - Rendtorff, Nanna Dahl

AU - Boulahbel, Houda

AU - Lodahl, Marianne

AU - Tranebjærg, Lisbeth

AU - Cesur, Yasar

AU - Dogan, Murat

AU - Yilmaz, Cahide

AU - Akgun, Cihangir

AU - Acikgoz, Mehmet

N1 - Copyright © 2011 Elsevier Masson SAS. All rights reserved.

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

KW - Adolescent

KW - Amino Acid Sequence

KW - Child

KW - Child, Preschool

KW - Chromosomes, Human, Pair 4

KW - Consanguinity

KW - Female

KW - HEK293 Cells

KW - Homozygote

KW - Humans

KW - Kidney Diseases

KW - Male

KW - Membrane Proteins

KW - Molecular Sequence Data

KW - Mutation

KW - Pedigree

KW - Turkey

KW - Wolfram Syndrome

KW - Young Adult

U2 - 10.1016/j.ejmg.2011.08.005

DO - 10.1016/j.ejmg.2011.08.005

M3 - Journal article

C2 - 21968327

SN - 1769-7212

VL - 55

SP - 37

EP - 42

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

IS - 1

ER -