Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro)
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Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro). / Yuca, Sevil Ari; Rendtorff, Nanna Dahl; Boulahbel, Houda; Lodahl, Marianne; Tranebjærg, Lisbeth; Cesur, Yasar; Dogan, Murat; Yilmaz, Cahide; Akgun, Cihangir; Acikgoz, Mehmet.
I: European Journal of Medical Genetics, Bind 55, Nr. 1, 2012, s. 37-42.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
Y1 - 2012
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
VL - 55
SP - 37
EP - 42
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
SN - 1769-7212
IS - 1
ER -
ID: 38380831